"When can I return to driving?": a review of the current literature on returning to driving after lower limb injury or arthroplasty.

Clinicians are often asked by patients, "When can I drive again?" after lower limb injury or surgery. This question is difficult to answer in the absence of any guidelines. This review aims to collate the currently available evidence and discuss the factors that influence the decision to allow a patient to return to driving. Medline, Web of Science, Scopus, and EMBASE were searched using the following terms: 'brake reaction time', 'brake response time', 'braking force', 'brake pedal force', 'resume driving', 'rate of application of force', 'driving after injury', 'joint replacement and driving', and 'fracture and driving'. Of the relevant literature identified, most studies used the brake reaction time and total brake time as the outcome measures. Varying recovery periods were proposed based on the type and severity of injury or surgery. Surveys of the Driver and Vehicle Licensing Agency, the Police, insurance companies in the United Kingdom and Orthopaedic Surgeons offered a variety of opinions. There is currently insufficient evidence for any authoritative body to determine fitness to drive. The lack of guidance could result in patients being withheld from driving for longer than is necessary, or returning to driving while still unsafe.

Parenting interventions for male young offenders: a review of the evidence on what works.

Approximately one in four incarcerated male young offenders in the UK is an actual or expectant father. This paper reviews evidence on the effectiveness of parenting interventions for male young offenders. We conducted systematic searches across 20 databases and consulted experts. Twelve relevant evaluations were identified: 10 from the UK, of programmes for incarcerated young offenders, and two from the US, of programmes for young parolees. None used experimental methods or included a comparison group. They suggest that participants like the courses, find them useful, and the interventions may improve knowledge about, and attitudes to, parenting. Future interventions should incorporate elements of promising parenting interventions with young fathers in the community, for example, and/or with older incarcerated parents. Young offender fathers have specific developmental, rehabilitative, and contextual needs. Future evaluations should collect longer-term behavioural parent and child outcome data and should use comparison groups and, ideally, randomization.

Anaphylaxis to the chlorhexidine component of Instillagel: a case series.

Anaphylaxis to chlorhexidine is rare. We report three cases of anaphylaxis attributed to the chlorhexidine component of Instillagel, presenting after urological surgery, while the patients were in the recovery room. In these cases, the cause of the collapse was not immediately obvious as the presentation was delayed. Anaesthetists should be aware that urethral lubricants may contain chlorhexidine that can trigger anaphylaxis in susceptible individuals. Anaphylaxis should be considered a possible diagnosis when a patient collapses in the recovery room. Investigation of suspected anaphylactic reactions related to anaesthesia is important to try and identify a likely trigger for a reaction and to help prevent further exposure and potential harm.

Knowledge gaps, attitude and beliefs of the communities about sickle cell disease in Eastern and Western Uganda.

BACKGROUND: The management of sickle cell disease (SCD) has remained insurmountable in developing countries such as Uganda, because most communities are not aware of it. OBJECTIVE: To determine knowledge gaps, attitudes and beliefs of the communities about sickle cell disease in Eastern and Western Uganda. DESIGN: Cross sectional descriptive study. SETTING: The districts of Sironko and Mbale in Eastern Uganda and Mbarara and Ntungamo in Western Uganda. SUBJECTS: Households, students and health workers. RESULTS: Household respondents from Eastern Uganda were more aware of SCD than those from Western (p < 0.001), with the majority reporting that they had seen more people with SCD in their communities than those from the West (p < 0.001). Fewer (< 1.9%) believed SCD was due to witch craft. Eight per cent of household respondents in Eastern believed it was a curse from God compared to 2% in the West. Less than 18% of the household respondents knew they could have children with SCD and (< 52%) of health workers knew SCD screening methods. Fewer (< 14%) of the health workers had participated in screening. Less than 20% of the respondents knew their sickle cell status. CONCLUSION: Respondents from Eastern Uganda were more aware of SCD than those from Western. Minority of the respondents knew their SCD status and few health staff knew how to screen it. There is need to sensitise communities and policy makers about prevention, screening and treatment of SCD.

Changes in expression of steroid receptors, their downstream target genes and their associated co-regulators during the sequential acquisition of tamoxifen resistance in vitro.

Tamoxifen resistance (TAMr) in breast cancer is a serious clinical dilemma, with no satisfactory explanation. We hypothesised that changes in the expression of steroid hormone receptors (ERalpha, ERbeta), their downstream target genes (PR, pS2) and their associated co-regulators (AIB-1, SRC-1, SRA, NCoR-1, SMRT and REA) could be related to the acquisition of TAMr. To test this hypothesis, we developed in vitro TAMr cell line models by continuous exposure of MCF-7 cells to 4-hydroxytamoxifen (4-HT) over 12 (MCF-7MMU1) and 21 (MCF-7MMU2) months, respectively and examined the expression of the above by Western blotting and immunohistochemistry. In addition, we further examined the changes in global gene expression in TAMr cells in comparison with TAM-sensitive cells by microarray analysis. We report here that acquisition of TAMr is associated with changes in the expression of PR, pS2 and several co-activators, but not ERs. In addition, genes associated with cell cycle, cell adhesion and extracellular matrix, were up-regulated while those associated with apoptosis or growth factors/hormones were down-regulated. Based on our results, it appears that increased co-activator expression, in concert with alterations in genes associated with controlling cell proliferation and survival contribute to TAMr in breast cancer.

Prevalence of thyroid antibodies in Nigerian patients.

BACKGROUND: Thyroid antibody testing is not routinely available in developing countries, and few studies have measured thyroid antibodies in Africans. The significance of thyroid autoimmunity in an African setting is thus unclear. AIM: To determine the prevalence of thyroid antibodies in patients attending a Nigerian teaching hospital. DESIGN: Prospective survey. METHODS: We measured antibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) using an ELISA technique in 104 patients with various thyroid pathologies attending an endocrine referral centre in Lagos, Nigeria. Patients were clinically grouped into Graves' disease (GD) (n = 69), simple non-toxic goitre (SNTG) (n = 21), toxic nodular goitre (TNG) (n = 8) and suspected Hashimoto's thyroiditis (HT) (n = 6). Blood donors without thyroid disease (n = 100) acted as controls. RESULTS: TgAb and TPOAb were found in 4% and 7%, respectively, of healthy adult controls, 11.6 and 76.8% of patients with GD, 25% and 12.5% of patients with TNG and 9.52% and 14.29% of patients with SNTG. TPOAb testing confirmed HT in six patients, and identified two further cases that would have been misdiagnosed without antibody testing. DISCUSSION: Thyroid autoimmunity appears more common in these Nigerian patients than in previous reports from Africa, and TPOAb was significantly associated with auto-immune thyroid disease. The clinical utility of these antibody measurements requires further evaluation in a wider African population.

Impact of a theoretically based sex education programme (SHARE) delivered by teachers on NHS registered conceptions and terminations: final results of cluster randomised trial.

OBJECTIVE: To assess the impact of a theoretically based sex education programme (SHARE) delivered by teachers compared with conventional education in terms of conceptions and terminations registered by the NHS. DESIGN: Follow-up of cluster randomised trial 4.5 years after intervention. SETTING: NHS records of women who had attended 25 secondary schools in east Scotland. PARTICIPANTS: 4196 women (99.5% of those eligible). INTERVENTION: SHARE programme (intervention group) v existing sex education (control group). MAIN OUTCOME MEASURE: NHS recorded conceptions and terminations for the achieved sample linked at age 20. RESULTS: In an "intention to treat" analysis there were no significant differences between the groups in registered conceptions per 1000 pupils (300 SHARE v 274 control; difference 26, 95% confidence interval -33 to 86) and terminations per 1000 pupils (127 v 112; difference 15, -13 to 42) between ages 16 and 20. CONCLUSIONS: This specially designed sex education programme did not reduce conceptions or terminations by age 20 compared with conventional provision. The lack of effect was not due to quality of delivery. Enhancing teacher led school sex education beyond conventional provision in eastern Scotland is unlikely to reduce terminations in teenagers. TRIAL REGISTRATION: ISRCTN48719575 [controlled-trials.com].

Peripheral cytokine expression in autoimmune thyroiditis: effects of in vitro modulation by rosiglitazone and dexamethasone.

BACKGROUND: In Hashimoto's thyroiditis (HT), there is evidence for activation of peripheral T-lymphocytes that predominantly express a T helper 1 (T(H)1) cytokine bias. However, the immunomodulatory factors involved in regulating this response have so far received scant attention. In this study, we examine the effects of the glucocorticoid, dexamethasone, and the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand, rosiglitazone on the expression of interferon (IFN)-gamma (T(H)1) and interleukin (IL)-4 (T(H)2) by activated peripheral CD4(+) and CD8(+) lymphocytes in patients with HT (n = 10) and healthy control subjects (n = 12). METHODS: Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with phorbolmyristate acetate (PMA) and ionomycin in the presence or absence of varying doses of dexamethasone and rosiglitazone (0.01 microM, 1.0 microM, and 100 microM). Cytokine expression was determined by flow cytometry. RESULTS: CD4(+) and CD8(+) IFN-gamma expression was greater in HT than controls (14.87 versus 9.25; p < 0.05 and 21.34 versus 10.16; p < 0.01, respectively). A dose-dependent inhibition of IFN-gamma expression was seen with dexamethasone and rosiglitazone. Inhibition of CD4(+) and CD8(+) IFN-gamma expression with both dexamethasone and rosiglitazone was greater in control subjects than in patients (p < 0.05). There was no significant difference in IL-4 expression between patients and control groups and its expression remained unaffected by either compound. CONCLUSIONS: We show that CD4(+) and CD8(+) T lymphocytes from HT patients express a type 1 cytokine bias that is significantly more resistant to in vitro modulation by rosiglitazone and dexamethasone. Further studies are needed to clarify if this resistance plays a role in the pathogenesis of autoimmune thyroid disease (AITD).

Thyroglobulin autoantibodies in iodized subjects: relationship between epitope specificities and longitudinal antibody activity.

INTRODUCTION: We previously reported a high thyroglobulin autoantibodies (TgAb) prevalence in healthy Sri Lankans after iodine supplementation. In the present study 58 TgAb-positive schoolgirls were followed up after 5 years of continued iodination. The objectives were: (1) to observe the longitudinal profile of TgAb epitope specificities and (2) to examine the relationship between these specificities and the course of thyroid autoimmunity in this population. METHODS: Paired subjects' sera (at onset and at 5-year follow-up) were tested for TgAb, thyroid peroxidase antibody (TPOAb), and TgAb epitope-specificity. Epitope reactivity was determined by employing a panel of 10 murine monoclonal antibodies (Tg-mAbs) directed against 6 Tg antigenic clusters (I-VI) in competitive enzyme-linked immunosorbent assay (ELISA) reactions with test sera. RESULTS: The overall pattern of epitope recognition in individual subject's sera remained preserved over the time period. Nine subjects showed restricted specificities while majority of the subjects were broadly heterogeneous. At follow-up, median TgAb concentration in the restricted group was higher than in the unrestricted (1650 versus 110 kIU/L; p < 0.005). Epitope specificity was a stronger determinant of TgAb persistence than the height of the initial TgAb response or the TPOAb status of subjects. CONCLUSION: Tg epitope reactivity pattern in iodised populations may identify subjects at greater risk of developing autoimmune thyroid disease (AITD).

Sequential studies on thyroid antibodies during pregnancy.

Thyroid antibodies were measured sequentially in 25 pregnant women from a Sri Lankan population. A high prevalence of antithyroid antibodies, particularly antithyroglobulin antibodies (TgAb) had previously been demonstrated in female schoolchildren drawn from this population. In the present study TgAb were detected in 36.8% of nonpregnant controls while thyroid peroxidase antibody (TPOAb) positivity was present in 26.3%. The prevalence of both antibodies in the pregnancy study group showed a progressive decline compared to nonpregnant controls throughout gestation becoming undetectable in the third trimester. The results are consistent with an immunosuppressive effect of pregnancy in a population in whom high thyroid autoantibody titers may have resulted from a recent salt iodization program.

Thyroid peroxidase antibodies in early pregnancy: utility for prediction of postpartum thyroid dysfunction and implications for screening.

Thyroid peroxidase antibodies (TPOAb) in pregnancy are a marker for postpartum (PPTD) and long-term thyroid dysfunction, with variable sensitivity and specificity in PPTD prediction. To test its utility in prediction, we recruited 308 TPOAb-positive (147 developed PPTD (PPTD group) and 161 remained euthyroid [PPTE group]) and 102 TPOAb-negative women (none developed PPTD), in early pregnancy (median, 18; range, 9-19 weeks' gestation). TPOAb levels were higher in the PPTD group (median) (125.2 kIU/L; p < 0.001), and in its hypothyroid (162.4 kIU.; p < 0.0001), hyperthyroid (114.2 kIU/L; p < 0.007), and biphasic (105.1 kIU/L; p < 0.02) variants, compared to the PPTE group (66.7 kIU/L) The incidence of PPTD was significantly higher with TPOAb levels above 58.2 kIU/L (early pregnancy versus postpartum; relative risk, 1.37 [95% confidence interval [CI] 1.17-1.61] versus 0.78 [95% CI 0.5-1.2]) compared to levels below. The integrated postpartum TPOAb response was higher in the PPTD group (median) (159 kIU/L per week) and its variants (hypothyroid; 199 kIU/L per week; biphasic, 180 kIU/L per week; hyperthyroid, 120 kIU/L per week), compared to the PPTE group (86 kIU/L per week p < 0.004). Median early pregnancy TPOAb levels in the PPTD and PPTE groups correlated well with the postpartum antibody response (r = 0.58, p < 0.001). The sensitivity of TPOAb in PPTD prediction was 100% (early pregnancy and postpartum), specificity 62% (early pregnancy) versus 41% (postpartum) and positive predictive value 48% (early pregnancy and postpartum). The timing of TPOAb testing, the sensitive assay used and the absence of PPTD in TPOAb-negative subjects contributed to this high sensitivity. We recommend TPOAb in early pregnancy as a useful predictor of PPTD, particularly in populations where PPTD does not occur in TPOAb-negative women.

High leptin levels in women developing postpartum thyroiditis.

BACKGROUND: There is experimental evidence that leptin is required for the development of T helper 1 (Th1)-mediated autoimmune diseases. However, to our knowledge, there are no studies demonstrating such a role in human autoimmune thyroid disease. OBJECTIVE: In the present study we have retrospectively examined patients developing postpartum thyroiditis (PPT), as a model of autoimmune disease, for changes in serum leptin levels during the postpartum period. MATERIALS AND METHODS: The study group included 61 women in the first month postpartum who were positive for thyroid peroxidase antibodies (TPOAb+ve). Twenty TPOAb-negative (-ve), age and body mass index (BMI)-matched, postpartum women were enrolled as the control group. All subjects were evaluated for BMI, serum leptin values, thyroid function [serum free-triiodiothyronine (FT3), free-thyroxine (FT4), thyrotropin (TSH)] and autoimmunity [TPOAb levels and complement activity index (C3 index)] at 4, 12, 16, 20 and 24 weeks' postpartum. During the postpartum period, 32 of 61 TPOAb+ve women (52.4%) showed one or more episodes of thyroid dysfunction (PPTD group), whereas the remaining 29 TPOAb+ve women remained euthyroid throughout the study period (PPTE group). None of the control group developed thyroid dysfunction. RESULTS: Four weeks postpartum, TPOAb+ve women showed higher serum leptin values than TPOAb-ve women, despite comparable BMI. At this time, PPTE and PPTD patients showed no significant differences in leptin levels or leptin/BMI ratio. Throughout the postpartum period, PPTD patients maintained significantly higher leptin values and leptin/BMI ratio compared to the healthy women. In PPTE women, however, a significant reduction in leptin levels and leptin/BMI ratio was seen at 12 weeks' postpartum. This decrease was transient and correlated negatively with the variation in C3 index at the same time. No significant correlation was found between serum leptin variations and FT4 or TSH levels. CONCLUSIONS: This study has demonstrated that women developing postpartum thyroiditis have higher leptin values compared to the healthy women. The higher levels were maintained for 6 months postpartum. This result would suggest an involvement of leptin in the pathogenesis of postpartum thyroid disease, although further studies are needed to characterize the reciprocal effects of leptin, immune system and thyroid hormones during the course of this disease.

Evolution of thyroid autoimmunity during iodine prophylaxis--the Sri Lankan experience.

OBJECTIVE: To study the evolution of thyroid autoimmunity, in relation to the change in goitre prevalence, during 3 Years of iodine prophylaxis in Sri Lanka. METHODS: Two groups of Sri Lankan schoolgirls between the ages of 10.8 and 17.5 Years were studied in 1998 (401 girls) and 2001 (282 girls). A prospective study was performed in 42 schoolgirls who were thyroid autoantibody (Ab)-positive (+ve) in 1998. Anthropometric measures, urinary iodine excretion (UIE), thyroid Volume, free thyroxine, free tri-iodothyronine, TSH, and thyroglobulin (Tg) and thyroid peroxidase (TPO) Ab were evaluated in all 683 girls. RESULTS: Goitre prevalence was significantly lower in 2001 compared with 1998 related to age (2.9% compared with 20.2%) and body surface area (11.6% compared with 40.8%), although UIE was unchanged. Prevalence of thyroid Ab in 2001 was also lower (23.4% compared with 49.9%); among those with the Ab, 34.8% had TgAb alone and 46.9% had a combination of TgAb+TPOAb, compared with 82.0% TgAb alone in 1998. In 2001, subclinical hypothyroidism was more frequent in Ab+ve (6.3%) than Ab-negative girls (1.0%). A cohort of 42 Ab+ve schoolgirls in 1998 (34 with TgAb alone, eight with TgAb+TPOAb) were evaluated again in 2001. Only 10 of them (23.8%) remained Ab+ve (mostly TPOAb+/-TgAb) in 2001. CONCLUSIONS: This study demonstrates that: (1) in 2001, goitre prevalence and thyroid autoimmunity rates were significantly lower than in 1998; (2) the pattern of thyroid Ab was different in the two surveys; (3) in 2001 alone, the occurrence of hypothyroidism was correlated with the presence of thyroid autoimmunity. These results indicate an evolution of thyroid autoimmune markers during the course of iodine prophylaxis, which has not been described before.

Thyroglobulin epitope recognition in a post iodine-supplemented Sri Lankan population.

OBJECTIVE: We previously reported a high prevalence of raised thyroglobulin autoantibodies (TgAb) in apparently healthy Sri Lankan schoolgirls following salt iodination. To characterize these antibodies further we determined the epitopes on thyroglobulin (Tg) with which they react and compared these with serum obtained from both healthy subjects and established autoimmune thyroid disease (AITD) patients from the UK. To extend our study to a wider population within Sri Lanka, we in addition determined the epitopes recognized by a group of AITD patients selected from a thyroid clinic in Sri Lanka, as well as apparently healthy female Sri Lankan tea workers of distinct ethnicity from the schoolgirls and AITD patients. DESIGN: Sri Lankan schoolgirls (n = 282) and adult female tea estate workers (n = 208) were examined for thyroid autoimmune markers. Sera with high TgAb (> 98 kIU/l) were selected from these two groups (n = 36 and 45, respectively) to study epitope-binding patterns. We also examined the sera from 16 AITD patients attending a thyroid clinic in Colombo, 16 patients with AITD from the thyroid clinic at the University Hospital of Wales and 16 sera from healthy control UK women with no evidence of thyroid disease. To determine the epitopes on Tg recognized by the subjects' TgAb, we employed a panel of Tg mouse monoclonal antibodies labelled with alkaline phosphatase in a competitive enzyme-linked immunosorbent assay reaction with the subjects' serum. RESULTS AND CONCLUSIONS: A majority of the Sri Lankan schoolgirls did not react with the immunodominant epitopes and did not differ significantly from healthy subjects from the UK in their Tg epitope recognition pattern. On the other hand, tea estate workers and Sri Lankan AITD patients recognized typical autoimmune thyroid disease epitopes and, in addition, recognized a separate cluster not previously associated with either the autoimmune state or the healthy state. The significance of this cluster requires further clarification.

Association of postpartum thyroid dysfunction with antepartum hormonal and immunological changes.

Postpartum thyroid dysfunction (PPTD) develops during the first 9 months in up to 50% of women who have thyroid peroxidase antibodies (anti-TPOAb +ve). Humoral immunity in PPTD has been well documented, but the cellular immunological events accompanying the Th2 to Th1 state postpartum are less clear. Peripheral blood lymphocyte cytokine secretion was examined in 48 TPOAb +ve and 33 TPOAb -ve women at 36 wk gestation and at 6, 12, and 24 wk postpartum. Eighteen women with PPTD had significantly greater secretion of interferon gamma and IL-4 than euthyroid women at 36 wk gestation with no significant differences in cytokine secretion at other time points. Also, at 36 wk gestation, the median plasma cortisol concentration in the PPTD group was significantly lower than the euthyroid group (442 nmol/liter vs. 567 nmol/liter, P < 0.02). There were no differences between the groups in levels of prolactin, progesterone, or estradiol. These data suggest that there may be less immunological suppression at 36 wk in TPOAb +ve women destined to develop PPTD possibly because of lower levels of cortisol. Thus, the immunological determinants of PPTD may in part occur antenatally, although the mechanism(s) for this is still unclear.