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1.  Maternal Smoking During Pregnancy and Intellectual Performance in Young Adult Swedish Male Offspring 
Smoking during pregnancy has been linked to an increased risk of several adverse birth outcomes. Associations with deficits in cognitive development have also been suggested. It is unclear if these associations are due to genetic and/or environmental confounding. In a population-based Swedish cohort study on 205 777 singleton males born to Nordic mothers between 1983 and 1988, we examined the association between maternal smoking during pregnancy and the risk of poor intellectual performance in young adult male offspring. In the cohort analyses, the risk of poor intellectual performance was increased in sons of smoking mothers compared to sons of non-smokers. Stratifying for maternal smoking habits across two pregnancies, there was an increased risk of poor intellectual performance for both sons if the mother was only smoking in the first pregnancy, but in neither son if the mother was only smoking in the second pregnancy. The effect of smoking during pregnancy on intellectual performance was not present when the association was evaluated within sibling pairs. Thus, the association between prenatal smoking exposure and offspring risk of low intellectual performance appears to be completely confounded by familial (genetic and early environmental) factors.
PMCID: PMC3653250  PMID: 20078833
2.  Molecular Techniques to Detect Biofilm Bacteria in Long Bone Nonunion: A Case Report 
Biofilms cause chronic infections including those associated with orthopaedic hardware. The only methods that are Food and Drug Administration-approved for detecting and identifying bacterial infections are cultures and selected DNA-based polymerase chain reaction methods that detect only specific pathogens (eg, methicillin-resistant Staphylococcus aureus). New DNA-based technologies enable the detection and identification of all bacteria present in a sample and to determine the antibiotic sensitivities of the organisms.
Case Description
A 34-year-old man sustained an open tibia fracture. He experienced 3 years of delayed healing and episodic pain. In addition to his initial treatment, he underwent three additional surgeries to achieve fracture healing. During the last two procedures, cultures were taken and samples were tested with the IBIS T5000 and fluorescence in situ hybridization (FISH). In both cases, the cultures were negative, but the IBIS and FISH confirmed the presence of a biofilm within the tibial canal.
Literature Review
Examinations of tissues from biofilm infections, by DNA-based molecular methods and by direct microscopy, have often found bacteria present despite negative cultures. Infections associated with orthopaedic hardware may be caused by bacteria living in biofilms, and these biofilm organisms are particularly difficult to detect by routine culture methods.
Purposes and Clinical Relevance
Rapid DNA-based detection methods represent a potentially clinically useful tool in the detection of bacterial biofilms. The sensitivity and clinical impact of the technology has yet to be established.
PMCID: PMC3183189  PMID: 21416206
3.  Orthopaedic biofilm infections 
Current orthopaedic practice  2011;22(6):558-563.
A recent paradigm shift in microbiology affects orthopaedic surgery and most other medical and dental disciplines because more than 65% of bacterial infections treated by clinicians in the developed world are now known to be caused by organisms growing in biofilms. These slime-enclosed communities of bacteria are inherently resistant to host defenses and to conventional antibacterial therapy, and these device-related and other chronic bacterial infections are unaffected by the vaccines and antibiotics that have virtually eliminated acute infections caused by planktonic (floating) bacteria. We examine the lessons that can be learned, within this biofilm paradigm, by the study of problems (e.g. non-culturability) shared by all biofilm infections and by the study of new therapeutic options aimed specifically at sessile bacteria in biofilms. Orthopaedic surgery has deduced some of the therapeutic strategies based on assiduous attention to patient outcomes, but much can still be learned by attention to modern research in related disciplines in medicine and dentistry. These perceptions will lead to practical improvements in the detection, management, and treatment of infections in orthopaedic surgery.
PMCID: PMC3272669  PMID: 22323927
chronic infection; biofilm; antibiotic resistance; surgical debridement; diagnosis
4.  Genetic Influences Are Important for Most But Not All Lower Urinary Tract Symptoms: A Population-Based Survey in a Cohort of Adult Swedish Twins 
European urology  2011;59(6):1032-1038.
The relative importance of genetic and environmental factors for the occurrence of lower urinary tract symptoms (LUTS) is poorly understood.
To (1) estimate the prevalence of urinary incontinence (UI), overactive bladder (OAB), and other LUTS and (2) to assess the heritability of these symptoms.
Design, setting, and participants
Cross-sectional survey of LUTS in a national population-based cohort of Swedish twins 20–46 yr of age (n = 42 582) from the Swedish Twin Registry.
Prevalence rates were determined and heritability of LUTS (in female twins) was assessed using indicators of twin similarity.
Results and limitations
A total of 25 364 twins completed the questionnaire (response rate: 59.6%). LUTS were more common in women (UI: 7%; OAB: 9%; nocturia: 61%; micturition frequency: 18%) than in men (UI: 1%; OAB: 5%; nocturia: 40%; micturition frequency: 11%), and prevalence increased with age. The strongest genetic effects were observed for UI, frequency, and nocturia. The lowest estimate for genetic effects was observed for OAB where environmental effects dominated, and more specifically shared family environment accounted for a third or more of the total variation. For stress UI, a fifth of the total variation in susceptibility to the disorder could be attributed to shared environment. Nonshared environmental effects were seen in the range of 45–65% for the various LUTS. The prevalence of LUTS was low in the men, and there were too few male cases to compute measures of similarity or heritability estimates.
This study provides robust evidence of a genetic influence for susceptibility to UI, frequency, and nocturia in women. In contrast, shared environmental factors seem more important for the predisposition to develop OAB, which may reflect familial patterns such as learning from parental behaviours.
PMCID: PMC3101479  PMID: 21420232
5.  Influence of smoking, coffee and tea consumption on bladder pain syndrome in female twins 
Urology  2011;77(6):1313-1317.
To assess the influence of smoking, coffee and tea consumption on the risk for bladder pain syndrome (BPS) using the O'Leary Interstitial Cystitis Symptom Index (ICSI)
In 2005, all twins born 1959–1985 in Sweden (n = 42 852) were invited to participate in a web-based survey to screen for complex diseases including BPS. Analyses were limited to female twins with information regarding bladder pain symptoms (n = 9 349). Women with an ICSI score of 6 or greater with required nocturia and bladder pain were defined as having BPS symptoms. Logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Environmental and genetic influences were assessed in co-twin control analysis
Tea consumption was associated with an increased risk for BPS (OR 1.26, 95% CI 1.02–1.55 for low tea consumption; OR 1.74, 95% CI 1.24–2.44 for high tea consumption). Coffee consumption was not a risk factor for BPS (OR 1.1, 95% CI 0.84–1.45). Former, and current smoking, were both associated with a higher risk of BPS (OR 1.5, 95% CI 1.18–1.89; and OR 1.49, 95% CI 1.16–1.92 respectively) but results from co-twin control analysis suggested that the association between smoking and BPS was confounded by familial factors.
Tea and smoking are environmental risk factors for BPS which are amenable to intervention. The effects of smoking on the risk for BPS may, however, be confounded by familial factors
PMCID: PMC3105162  PMID: 21439616
Bladder pain syndrome; Coffee; Smoking; Tea; Twins
6.  Outcomes of Nonoperatively Treated Displaced Scapular Body Fractures 
Displaced scapular body fractures most commonly are treated conservatively. However there is conflicting evidence in the literature regarding the outcomes owing to retrospective design of studies, different classification systems, and diverse outcome tools.
The functional outcome after nonoperative management of displaced scapular body fractures was assessed by change in the DASH (Disability of Arm, Shoulder and Hand) score; (2) the radiographic outcome was assessed by the change of the glenopolar angle (GPA); and (3) associated scapular and extrascapular injuries that may affect outcome were identified.
Patients and Methods
Forty-nine consecutive patients were treated with early passive and active ROM exercises for a displaced scapular body fracture. We followed 32 of these patients (65.3%) for a minimum of 6 months (mean, 15 months; range, 6–33 months). Mean age of the patients was 46.9 years (range, 21–84 years) and the mean Injury Severity Score (ISS) was 21.5 (range, 5–50). Subjective functional results (DASH score) and radiographic assessment (fracture union, glenopolar angle) were measured.
All fractures healed uneventfully. The mean change of glenopolar angle was 9° (range, 0°–20°). The mean change of the DASH score was 10.2, which is a change with minimal clinical importance. There was a correlation between the change in this score with the ISS and presence of rib fractures.
Satisfactory outcomes are reported with nonoperative treatment of displaced scapular body fractures. We have shown that the severity of ISS and the presence of rib fractures adversely affect the clinical outcome.
Level of Evidence
Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC3069270  PMID: 21161746
7.  Diabetes and Obesity-Related Risks for Pelvic Reconstructive Surgery in a Cohort of Swedish Twins  
Diabetes Care  2008;31(10):1997-1999.
OBJECTIVE—To determine the diabetes- and obesity-related risks for surgically managed stress urinary incontinence and pelvic organ prolapse.
RESEARCH DESIGN AND METHODS—This twin cohort study used the Swedish Twin Register to identify 8,443 female twin pairs born from 1926 through 1958. The association between diabetes and pelvic floor surgery was estimated while taking into account the correlated (twin) structure of the data.
RESULTS—For type 1 and type 2 diabetes, no significant associations were observed for stress urinary incontinence (odds ratio [OR] 1.0 [95% CI 0.1–9.2] and 2.0 [1.0–4.0], respectively). There were no cases of prolapse surgery in type 1 diabetic subjects, and for type 2 diabetes the risk estimate was nonsignificant (1.6 [1.0–2.7]). BMI >25 kg/m2, age ≥60 years, and childbirth were the strongest risk factors for having incontinence surgery.
CONCLUSIONS—Our data suggest that diabetes is not associated with stress urinary incontinence or pelvic organ prolapse surgery.
PMCID: PMC2551642  PMID: 18628571
8.  Specificity and Function of Immunogenic Peptides from the 35-Kilodalton Protein of Mycobacterium leprae 
Infection and Immunity  1999;67(3):1501-1504.
We identified a T-cell determinant of the 35-kDa antigen of Mycobacterium leprae which is discriminatory against cross-sensitization by its closely related homologue in Mycobacterium avium. From synthetic peptides covering the entire sequence, those with the highest affinity and permissive binding to purified HLA-DR molecules were evaluated for the stimulation of proliferation of peripheral blood mononuclear cells (PBMCs) from leprosy patients and healthy sensitized controls. Responses to the peptide pair 206–224, differing by four residues between M. leprae and M. avium, involved both species-specific and cross-reactive T cells. Lymph node cell proliferation in HLA-DRB1*01 transgenic mice was reciprocally species specific, but only the response to the M. leprae peptide in the context of DR1 was immunodominant. Of the cytokines in human PBMC cultures, gamma interferon production was negligible, while interleukin 10 (IL-10) responses in both patients and controls were more pronounced. IL-10 was most frequently induced by the shared 241–255 peptide, indicating that environmental cross-sensitization may skew the response toward a potentially pathogenic cytokine phenotype.
PMCID: PMC96486  PMID: 10024600

Results 1-8 (8)