Smoking and disease severity in rheumatoid arthritis: Association with polymorphism at the glutathione S‐transferase M1 locus

Objective

To determine whether the relationship between smoking and disease severity in women with rheumatoid arthritis (RA) is associated with polymorphism at the glutathione S‐transferase (GST) M1 locus.

Methods

Genotyping for GSTM1 was carried out using polymerase chain reaction methodology on 164 women with established RA. Smoking history was obtained on each patient. Radiographic damage was measured by the Larsen score, and functional outcome was assessed by the Health Assessment Questionnaire (HAQ). Data were analyzed by multiple regression analyses, with correction for age and disease duration.

Results

Ever having smoked was associated with a worse radiographic and functional outcome than was never having smoked. Both past and current smoking were associated with increased disease severity. Stratification by GSTM1 status revealed that polymorphism at this locus affected the relationship between smoking and disease outcome measures. Patients who lacked the GSTM1 gene and had ever smoked had significantly higher Larsen and HAQ scores than did those who lacked the gene and had never smoked. Radiographic outcome in these patients was worse than that in patients who had the GSTM1 gene and who had smoked. The associations were not affected by correction for socioeconomic status. Rheumatoid factor (RF) production was found to be associated with smoking in only the GSTM1‐null patients.

Conclusion

Our data suggest that disease outcome in female RA patients with a history of smoking is significantly worse than in those who have never smoked. Smoking was associated with the most severe disease in patients who carried the GSTM1‐null polymorphism. This association may be due in part to a relationship between the GSTM1 polymorphism and RF production in smokers.

     

The prevalence of pain at pressure areas and pressure ulcers in hospitalised patients

Background

Patients with pressure ulcers (PUs) report that pain is their most distressing symptom, but there are few PU pain prevalence studies. We sought to estimate the prevalence of unattributed pressure area related pain (UPAR pain) which was defined as pain, soreness or discomfort reported by patients, on an “at risk” or PU skin site, reported at a patient level.

Methods

We undertook pain prevalence surveys in 2 large UK teaching hospital NHS Trusts (6 hospitals) and a district general hospital NHS Trust (3 hospitals) during their routine annual PU prevalence audits. The hospitals provide secondary and tertiary care beds in acute and elective surgery, trauma and orthopaedics, burns, medicine, elderly medicine, oncology and rehabilitation. Anonymised individual patient data were recorded by the ward nurse and PU prevalence team. The analysis of this prevalence survey included data summaries; no inferential statistical testing was planned or undertaken. Percentages were calculated using the total number of patients from the relevant population as the denominator (i.e. including all patients with missing data for that variable).

Results

A total of 3,397 patients in 9 acute hospitals were included in routine PU prevalence audits and, of these, 2010 (59.2%) patients participated in the pain prevalence study. UPAR pain prevalence was 16.3% (327/2010). 1769 patients had no PUs and of these 223 patients reported UPAR pain, a prevalence of 12.6%. Of the 241 people with pressure ulcers, 104 patients reported pain, a UPAR pain prevalence of 43.2% (104/241).

Conclusion

One in six people in acute hospitals experience UPAR pain on ‘at risk’ or PU skin sites; one in every 8 people without PUs and, more than 2 out of every five people with PUs. The results provide a clear indication that all patients should be asked if they have pain at pressure areas even when they do not have a PU.

     

Early posttranslational modifications of the three neurofilament subunits in mouse retinal ganglion cells: neuronal sites and time course in relation to subunit polymerization and axonal transport

We have characterized stages in the posttranslational processing of the three neurofilament subunits, High (NF-H), Middle (NF-M), and Low (NF-L), in retinal ganglion cells in vivo during the interval between synthesis in cell bodies within the retina and appearance of these polypeptides in axons at the level of the optic nerve (optic axons). Neurofilament proteins pulse-labeled by injecting mice intravitreally with [35S]methionine or [32P]orthophosphate, were isolated from Triton-soluble and Triton-insoluble fractions of the retina or optic axons by immunoprecipitation or immunoaffinity chromatography. Within 2 h after [35S]methionine injection, the retina contained neurofilament-immunoreactive radiolabeled proteins with apparent molecular weights of 160, 139, and 70 kDa, which co-migrated with subunits of axonal neurofilaments that were dephosphorylated in vitro with alkaline phosphatase. The two larger polypeptides were not labeled with [32P]orthophosphate, indicating that they were relatively unmodified forms of NF-H and NF-M. About 75% of the subunits were Triton-insoluble by 2 h after isotope injection, and this percentage increased to 98% by 6 h. Labeled neurofilament polypeptides appeared in optic axons as early as 2 h after injection. These subunits exhibited apparent molecular weights of 160, 139, and 70 kDa and were Triton-insoluble. The time of appearance of fully modified polypeptide forms differed for each subunit (2 h for NF-L, 6-18 h for NF-M, 18-24 h for NF-H) and was preceded by the transient appearance of intermediate forms. The modified radiolabeled subunits in optic axons 3 days after synthesis were heavily labeled with [32P]orthophosphate and exhibited the same apparent molecular weights as subunits of axonal neurofilaments (70 kDa, 145 and 140 kDa, and 195-210 kDa, respectively). Whole mounts of retina immunostained with monoclonal antibodies against NF-H in different states of phosphorylation demonstrated a transition from non-phosphorylated neurofilaments to predominantly phosphorylated ones within a region of the axon between 200 and 1000 microns downstream from the cell body. These experiments demonstrate that the addition of most phosphate groups to NF-M and NF-H takes place within a proximal region of the axon. The rapid appearance of modified forms of NF-L after synthesis may imply that processing of this subunit occurs at least partly in the cell body. The presence of a substantial pool of Triton-insoluble, unmodified subunits early after synthesis indicates that the heaviest incorporation of phosphate occurs after neurofilament proteins are polymerized.(ABSTRACT TRUNCATED AT 400 WORDS)     

Determining Sleep Quality in Children with Sleep Disordered Breathing: EEG Spectral Analysis Compared with Conventional Polysomnography

Study Objectives:

To identify the extent of sleep disruption in children with various severities of sleep disordered breathing (SDB) using both conventional visually scored assessment of sleep stages and arousal indices together with EEG power spectral analysis.

Design:

Sleep stages and power spectral analysis of the sleep EEG in children with varying severities of SDB with matched control subjects with no history of snoring were compared across the whole night, across sequential hours from sleep onset, and across sleep stages.

Measurements:

Overnight polysomnography was performed on 90 children (49M/41F) aged 7-12 y with SDB and 30 age-matched healthy controls (13M/17F). Sleep stages were visually scored and the EEG spectra were analyzed in 5-s epochs.

Results:

Conventional visual scoring indicated that, although sleep duration was reduced in severely affected children, sleep quality during the essential stages of SWS and REM was preserved, as evidenced by the lack of any significant decrease in their duration in SDB severity groups. This finding was supported by the lack of substantial differences in EEG spectral power between the groups over the whole night, within specific hours, and in individual sleep stages.

Conclusions:

Both conventional scoring and EEG spectral analysis indicated only minor disruptions to sleep quality in children with SDB when assessed across the night, in any specific hour of the night, or in any specific sleep stage. These results suggest that reduced daytime functioning previously reported in children with SDB may not be due to sleep disruption. We speculate that in children, in contrast to adults, a stronger sleep drive may preserve sleep quality even in severe SDB.

Citation:

Yang JSC; Nicholas CL; Nixon GM; Davey MJ; Anderson V; Walker AM; Trinder JA; Horne RSC. Determining sleep quality in children with sleep disordered breathing: EEG spectral analysis compared with conventional polysomnography. SLEEP 2010;33(9):1165-1172.     

Quiescent T cells and HIV: an unresolved relationship

The ability of HIV to infect quiescent CD4⁺ T cells has been a topic of intense debate. While early studies suggested that the virus could not infect this particular T cell subset, subsequent studies using more sensitive protocols demonstrated that these cells could inefficiently support HIV infection. Additional studies showed that the kinetics of infection in quiescent cells was delayed and multiple stages of the viral life cycle were marred by inefficiencies. Despite that, proviral DNA has been found in these cells presenting them as a potential viral reservoir. Therefore, a better understanding of the relationship between HIV and quiescent T cells may lead to further advances in the field of HIV.     

Short sleep duration in middle childhood: risk factors and consequences

STUDY OBJECTIVES: To measure sleep duration in 7-year-old children; identify the determinants of sleep duration; and assess the association between short sleep duration and obesity, cognitive functioning, and behaviour. DESIGN: Longitudinal study with disproportionate sampling of the participants. SETTING: Community. PARTICIPANTS: 591 seven-year-old children, of whom 519 had complete sleep data. INTERVENTIONS: Not applicable. MEASUREMENTS: Sleep duration was assessed by actigraphy. Other measurements included height, weight, BMI, percentage body fat as assessed by bioimpedance assay, intelligence (WISC-III) and behaviour (Strengths & Difficulties questionnaire, parent and teachers Conners Rating Scales). RESULTS: Mean time in bed according to parental report was 10.9 hours (SD 0.8). Mean sleep duration by actigraphy was 10.1 (SD 0.8) hours. In multivariable analysis, sleep duration was longer on weekdays vs. weekend nights (31.5 min, P = 0.002), in winter (40.5 min), autumn (31.1 min), and spring (14.8 min) compared with summer (P <0.0001), and in those with younger siblings (11.7 min, P = 0.03). Sleep duration was shorter when bedtime was after 21:00 (-41.1 min, P <0.0001). In multivariable analysis, sleep duration <9 hours was associated with being overweight/ obese (BMI: OR = 3.32; 95% CI = 1.40, 7.87) with an increase of 3.34% body fat (P = 0.03), and this was not explained by physical activity or television watching. Short sleep duration was also associated with higher emotional lability scores (Conners Rating Scale Parent Form; P = 0.03). IQ (WISC-III) and attention deficit / hyperactivity disorder scores (both parent and teachers Conners Rating Scales) did not differ with sleep duration. CONCLUSIONS: Sleep duration in 7-year-old children varies considerably among individuals. The duration is affected by weekday, season, and having younger siblings. Importantly, short sleep duration was shown to be an independent risk factor for obesity/overweight.     

Anthropometric measurements of children attending a vaccination clinic in Yaounde, Cameroon

Background

Growth faltering is a frequent public health problem in children and anthropometric measurements are useful tools for follow-up and early diagnosis. This problem has not been studied in the Cameroonian setting, that''s why we undertook this study.

Objectives

To have a synopsis of the nutritional status in apparently healthy children attending a vaccination clinic and show the importance of anthropometric measurements in routine child health care.

Design

A retrospective study.

Patients and Participants

1351 children aged (6–24months), who attended the vaccination clinic of the Yaounde Gynaeco-Obstetric and Pediatric Hospital over a 6 month period, were enrolled in the study.

Method

The registers of the vaccination clinic of the above hospital were retrospectively reviewed from 1^st March to 31^st August 2005. The following parameters were noted: age, height, weight, mid-upper arm circumference (MUAC), and Z scores calculated for the following indicators: weight for age (WAZ), weight for height (WHZ), and height for age (HAZ).

Results

Our results show that 12 children (1.1percent) in the 0–6 months age group and 4 (1.6 percent) in the 6–12 months age group had WAZ less than -2 indicating underweight. Also 10 children (0.9 percent) and 2 (0.8 percent) in the 0–6 and 6–12 months age groups respectively had WHZ less than −2, indicating wasting. HAZ was less than −2 in 70 children (6.4 percent) and in 8 (3.2 percent) in the 0–6 and 6–12 months age groups respectively indicating stunting. The MUAC was less than 12.5 cm in 6 children (2.4 percent).

Conclusions

From our results, we conclude that growth faltering is common in supposedly healthy children attending our vaccination clinic. Anthropometric measurements are thus recommended and should be encouraged in routine child care settings for early diagnosis of growth retardation and to provide useful interventions.