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Hereditary breast cancer accounts for up to 5-10% of all breast carcinomas. Recent studies have demonstrated that mutations in two high-penetrance genes, namely BRCA1 and BRCA2, are responsible for about 16% of the familial risk of breast cancer. Even though subsequent studies have failed to find another high-penetrance breast cancer susceptibility gene, several genes that confer a moderate to low risk of breast cancer development have been identified; moreover, hereditary breast cancer can be part of multiple cancer syndromes. In this review we will focus on the hereditary breast carcinomas caused by mutations in BRCA1, BRCA2, Fanconi anaemia (FANC) genes, CHK2 and ATM tumour suppressor genes. We describe the hallmark histological features of these carcinomas compared with non-hereditary breast cancers and show how an accurate histopathological diagnosis may help improve the identification of patients to be screened for mutations. Finally, novel therapeutic approaches to treat patients with BRCA1 and BRCA2 germ line mutations, including cross-linking agents and PARP inhibitors, are discussed. [ABSTRACT FROM AUTHOR]

Aim: To study the prevalence, type, and progression of astigmatism in Chinese preschool children, and its effect on refractive development. Methods: A cross sectional study of preschool children was carried out in two randomly selected kindergartens. A cohort study was performed on a subset of children, five years after initial examination. Refractive error (measured by cycloplegic auto refraction) and axial ocular dimensions (measured by ultrasonography) were the main study outcomes. Results: 522 children participated in the study; the mean age was 55.7 months (SD 10.9; range 27 to 77). Mean cylinder reading was -0.65 D (SD 0.58; range 0.00 to -4.75), and with the rule astigmatism was predominant (53%). In the 108 children studied longitudinally, the mean cylinder reading reduced from -0.62 D to -0.50 D (p=0.019). The presence of astigmatism in initial examination predisposed the eyes towards greater myopisation (p<0.001). In addition, children with increased astigmatism had greater myopic progression (p<0.001) and axial length growth (p = 0.002). Conclusions: This study reports a high prevalence of astigmatism in Chinese preschool children. The presence of astigmatism, and particularly with increasing astigmatism, appears to predispose the children to progressive myopia. Further studies are warranted. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine whether men who grew slowly in utero or during infancy are more vulnerable to the later effects of poor living conditions on coronary heart disease. Design: Follow up study of men for whom there were data on body size at birth and growth and social class during childhood, educational level, and social class and income in adult life. Setting: Helsinki, Finland. Participants: 3676 men who were born during 1934-44, attended child welfare clinics in Helsinki, were still resident in Finland in 1971, and for whom data from the 1980 census were available. Main outcome measures: Hospital admission for or death from coronary heart disease. Results: Men who had low social class or low household income in adult life had increased rates of coronary heart disease. The hazard ratio among men with the lowest annual income (<£8400) was 1.71 (95% confidence interval 1.18 to 2.48) compared with 1.00 in men with incomes above £15 700. These effects were stronger in men who were thin at birth (ponderal index < 26 kg/m³): hazard ratio 2.58 (1.45 to 4.60) for men with lowest annual income. Among the men who were thin at birth the effects of low social class were greater in those who had accelerated weight gain between ages 1 and 12 years. Low social class in childhood further increased risk of disease, partly because it was associated with poor growth during infancy. Low educational attainment was associated with increased risk, and low income had no effect once this was taken into account. Conclusion: Men who grow slowly in utero remain biologically different to other men. They are more vulnerable to the effects of low socioeconomic status and low income on coronary heart disease. [ABSTRACT FROM AUTHOR]

Among 4630 boys, irrespective of the social class into which they were born, those grew slowly during infancy had poor poor educational achievement and had lower incomes than those who grew rapidly. One interpretation of this is that biological processes linked to slow infant growth may lead to lifelong impairment of cognitive function. [ABSTRACT FROM AUTHOR]

The aim of this glossary is to define some key terms used in the field of developmental and life course epidemiology. [ABSTRACT FROM AUTHOR]

Background and aims: Allograft rejection is the commonest cause of corneal transplant failure and is significantly higher in high-risk patients. Corneal tissue is reported to produce chemokines in response to stress! inflammation. Expression of chemokines is central to the recruitment of leucocytes during inflammatory events. This study was designed to evaluate the effects of surgical trauma or storage conditions on chemokine expression. Methods: Murine corneas were manipulated by incubation in different conditions for up to 24 h, by the addition of endotoxin or by surgical trauma. The ex vivo production of chemokines was assessed using a real-time reverse- transcriptase PCR (RT-PCR) assay to measure mRNA encoding MlP-1α, MIP-1β and MIP-1γ, MCP1, IP-10, lymphotactin, fractalkine, RANTES, eotaxin, MIG, MIP2 and the cytokine MIF. The expression of RANTES was also determined by ELISA, and the ability of supernatant from corneas on chemotaxis of cells was also determined. Finally, we compared the survival of corneal grafts that had (or had not( been treated with endotoxin. Results: We found that on incubation in corneal storage medium, expression of mRNA for the majority of these chemokines greatly increased. Upregulation of chemokine mRNA expression was also seen following the mechanical trauma of suture insertion and exposure of the cornea to endotoxin. In the case of mechanical trauma, functional activity of the chemokines was demonstrated using a chemotaxis assay. Orthotopic transplantation of LPS-treated corneas, in which chemokine expression was elevated, resulted in increased infiltration by leucocytes and more rapid rejection of allogeneic grafts. Conclusion: Our results indicate that ex vivo storage and manipulation of murine corneas can influence the expression of chemokines in corneas, and can result in earlier graft rejection. This may be of importance when considering procedures for manipulation and ex vivo storage of donor corneas prior to transplantation, as well as the surgical procedure itself. [ABSTRACT FROM AUTHOR]

Objective: To determine the path of growth of girls who later develop coronary heart disease.Design: Follow up study of girls whose body size at birth, during infancy, and childhood up to age 12 years was recorded.Setting: Helsinki, Finland.Participants: 4130 girls who were born between 1934 and 1944, attended child welfare clinics in Helsinki, and were still resident in Finland in 1971.Main Outcome Measure: Hospital admission or death from coronary heart disease.Results: In comparison with boys in the same cohort who later developed coronary heart disease the 87 girls were short at birth, rather than thin, had compensatory growth in height during infancy, became thin, and thereafter had a rapid increase in weight and body mass index. In a combined analysis the hazard ratios for coronary heart disease were 1.17 (95% confidence interval (CI) 1.03 to 1.32, p = 0.02) for each 1 cm decrease in length at birth, 1.52 (95% CI 1.23 to 1.89, p < 0.001) for each standard deviation score increase in body mass index after age 3 years, and 1.63 (95% CI 1.09 to 2.42, p = 0.02) for each decrease in level of education.Conclusions: Though broadly similar, the paths of growth associated with the later development of coronary heart disease differ in girls and boys. This may be because girls are less vulnerable to undernutrition in utero and are better able to sustain postnatal growth in an adverse environment. [ABSTRACT FROM AUTHOR]

Comments on the time lag hypothesis explaining low mortality rates from coronary heart disease in France. Explanation on the intrauterine nutrition theory; Details on the history of malnutrition that befell France and Great Britain; Effect of better nutrition in pregnancy.

OBJECTIVE: To identify the experience, opinions and recommendations of pharmacists when dispensing hospital generated prescriptions in community pharmacy. METHODS: Descriptive, cross-sectional, prepiloted, self-administered postal survey sent from Birmingham Children''s Hospital (BCH) to community pharmacists known to have dispensed hospital prescriptions (HPs) issued by BCH during June 2008 to May 2009 (n=1282). Survey commenced 22nd September 2009 with two reminders if necessary. The 48 point questionnaire included: demographics; experience and opinions concerning problems when dispensing hospital prescriptions; sources of further information and improving existing arrangements. Responses were entered into SPSS v16 for analysis. RESULTS: Response rate of 47.3% (n=607). Length of experience of the respondents working as community pharmacists ranged from 0 to 44 years with median 14 years. Overall approximately 0.3% of prescriptions dispensed or supervised by respondents were HPs, considerably lower than the national average of 0.6% (personal communication). Time to dispense HPs (mean 8.15 min, SD 9.86, median 5 min) was significantly different (p < 0.001) to GP prescriptions (mean 3.37 min, SD 2.86, median 2 min). There is a significant positive correlation (p = 0.002) between the experience of respondents dispensing HPs and the additional time they take to dispense HPs in comparison to GP prescriptions. When asked the question ‘In comparison to an average GP prescription what is the likelihood of problems when dispensing a HP in a community pharmacy?’ 87.4% (n=528) replied more or much more. Commonly reported problems include: illegible prescriptions, unfamiliar drug and missing information on the prescription, for example, quantity. The problems seem unrelated to unlicensed drugs. 61.1% (n=368) believe that there is more risk of error when dispensing a HP compared to a GP prescription. Pharmacists needing further advice were likely or very likely to consult a standard text (84.7%), the hospital prescriber (84%) or the prescriber''s support staff (67.3%). The study estimates the frequency of calls to prescribers made by respondents with 1 call for 923 GP prescriptions compared to 1 call for 10.7 HPs: quantifying observations in a published audit.1Recommended service improvements are (1) include direct contact details of prescriber on prescription forms and (2) ensure prescriptions are printed. CONCLUSION: Community pharmacists report frequent problems when dispensing HPs and a higher risk of error in comparison to dispensing GP prescriptions. As a consequence average dispensing time is more than doubled for HPs. Calls to HP prescribers are proportionally much more frequent than to GPs. Greater experience of dispensing HPs prompts longer dispensing times for HPs. Recommended service improvements are print prescriptions and include contact details of prescriber on the prescription form. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To identify the involvement and opinions of hospital medical staff in supporting medication access for paediatric home-patients. We define a home-patient as a patient not in hospital and largely cared for by primary care services where prescribing responsibility remains with the GP. METHODS: Descriptive, cross-sectional survey using an electronic questionnaire constructed and piloted with the support of hospital doctors, using LimeSurvey software (version 1.71) and sent via hospital email addresses to all medical staff (n=340) at Birmingham Children''s Hospital. The survey was tokenised to ensure that one invitation elicited one response only and sent commencing January 2010 with two reminders if necessary. The 30 point questionnaire included: demographics; frequency of prescribing; reasons for medication access problems; interaction with community pharmacists; and improving current arrangements. Responses were entered into MS Excel 2003 and SPSS v16 for analysis. Service costs are based on a fee of £26 per telephone consultations: confirmed as appropriate by the Department of Health (Commissioning Department Birmingham Children''s Hospital to D Terry, personal communication). RESULTS: Response rate of 48.5% (n=165) from 24 paediatric specialties. Nearly half of respondents (n=81) wrote urgent prescriptions for home-patients in a 3 month period. Respondents providing this service describe the clinical risk to patients if they did not provide this service as: small 9.2% (n=7); moderate 46.1% (n=35); high 35.5% (n=27); very high 9.2% (n=7). Respondents were asked to identify the most likely reason for medication access problems from a list of possible reasons with the following results: GP issue 44.5% (n=65); Communication issue 17.1% (n=25); Carer issue 13.0% (n=19); Pharmacy issue 6.2% (n=9); Formulation issue 1.4% (n=2). Respondents were asked to assess the likelihood (very unlikely, quite unlikely, sometimes, quite likely, very likely) of a list of possible reasons why GPs may decline to provide repeat prescriptions for children with the following results for very likely or quite likely: clinical concerns 56% (n=84); communication issues 52% (n=78); PCT influence 47.3% (n=71). Annual service costs for this institution are estimated as £120 000. CONCLUSION: Hospital doctors act frequently to assist paediatric patients outside hospital who are largely cared for by primary care services (home-patients) to obtain the medicines they need. This activity is not covered by existing contractual arrangements between the hospital and PCTs. The most common reason for this activity cited by respondents is GP issues, prompted by clinical concerns. Require GPs to prescribe all continuing medicines was considered to be a high or very high benefit by over 60% of respondents: a view similar to that of hospital nurses.1Hospital and community pharmacists will benefit from being aware of this activity, perceived clinical importance and service costs. [ABSTRACT FROM AUTHOR]

The article discusses a study to find out if a pharmacist-led pediatric commissioning service was more effective in getting individual funding requests (IFR) for Primary Care Trusts (PCTS), and reports that it improves the chances of doing so by 73%.

The article discusses a study to determine how general practitioners and nurses in Britain felt about providing medication to pediatric patients outside their facilities. It states that the study was done through online surveys filled out by staff at the Birmingham Children's Hospital starting in January 2010. Besides their opinions on the practice, they were also asked how such could be improved. Findings showed that almost half prescribed medication to those receiving home care, support the practice, but are wary of the risks when they are not present.

The article discusses a study to determine the efficacy of community pharmacists in dispensing hospital prescription (HP) drugs, explains the methodology involved in conducting the study, and cites findings which show that the error rate was higher compared to those given out by general practitioners, resulting in the former calling the latter more frequently for confirmation, increasing the dispensing time considerably.

Aims: To study the ocular manifestations and their severity in children with Graves’ disease. Methods: All patients with Graves’ disease having regular follow up in a paediatric endocrine clinic were recruited for the study. A comprehensive ophthalmic assessment including ocular motility, exophthalmometry, intraocular pressure (IOP), slit lamp, and fundus examinations was performed. Results: 83 patients (72 female, 11 male) aged 16 years or below were examined. All are Chinese. Ocular symptoms occurred in 12 patients. Ocular signs of ophthalmopathy were documented in 52 patients (62.7%). Most of them presented with eyelid abnormalities such as lid oedema, lid lag, and lagophthalmos, whereas lower lid retraction was the commonest clinical sign noted (38.6%). Diffuse conjunctival injection was found in four patients (4.8%). 10 patients (12.0%) had mild proptosis of less than 3 mm. Only one patient (1.2%) had limited extraocular motility in extreme gaze. Punctate epithelial corneal erosions were reported in 11 patients (13.3%). Conclusions: This is the largest series on the ocular complications of childhood Graves’ disease in the literature. Although 52 patients (62.7%) were identified with positive ocular changes, none of them had visual threatening complications or debilitating myopathy. [ABSTRACT FROM AUTHOR]

Background People who score poorly in intellectual ability tests have shorter life expectancy. A study was undertaken to determine whether this association is different in people from different socioeconomic backgrounds. Methods The mortality of 2786 men born in Helsinki, Finland during 1934-1944 who, as military conscripts, underwent a standardised intellectual ability test comprising verbal, visuospatial and arithmetic reasoning subtests was studied. Mortality data came from the Finnish Death Register. Results Comparing men in the lowest and highest test score quartiles, HRs for all-cause mortality were 1.9 (95% CI 1.4 to 2.5) for verbal reasoning, 2.2 (95% CI 1.6 to 3.0) for visuospatial reasoning and 1.9 (95% CI 1.4 to 2.5) for arithmetic reasoning, corresponding to 2.6, 3.4 and 2.6 excess years of life lost, respectively. Associations were similar for cardiovascular and noncardiovascular mortality. Intellectual ability scores were stronger predictors in men who grew up in middle-class families. Compared with middle-class men in the highest quartile of the visuospatial reasoning score, middle-class men in the lowest quartile lost 6.5 years of life while men from families of manual workers in the highest quartile lost 2.8 years and men in the lowest quartile lost 5.6 years. Conclusions High intellectual ability in men aged 20 protects them from mortality in later life. This effect is stronger in men who grew up in middle-class families than in those who grew up in manual worker families. This finding suggests that early life conditions that are unfavourable to the development of cognitive abilities negate the life expectancy benefits of being born into a more affluent family. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the visual and fluorescein angiographic outcomes of photodynamic therapy (PDT) with verteporfin in patients with subfoveal choroidal neovascularisation (CNV) caused by pathologic myopia in the Chinese. Methods: Prospective, non-comparative, two centre interventional study. Patients with CNV secondary to pathologic myopia of Chinese ethnicity were recruited and treated with a standard regimen of PDT with verteporfin. Results of this study in Chinese eyes with pigmented retinal pigment epithelium were compared with those from the Verteporfin in Photodynamic Therapy (VIP) Study of predominantly white eyes. Results: Thirty one and 22 eyes that completed the 12 month and 24 month follow up studies respectively were analysed. The mean and median best corrected visual acuities (BCVA) could be maintained at the baseline level at the 12 month and 24 month visits. Fourteen (63.6%) eyes had stable or improved BCVA at 24 months and six (27.3%) of them had a moderate gain in vision (improved by three or more lines). Visual results were comparable with that of the VIP study, but the average accumulative PDT treatments required in one and two years were 1.7 and 2.3 respectively, which were significantly less than 3.4 and 5.1 treatments in VIP study. Mean logMAR BCVA of the younger age group (<55 years) at 24 months was 0.41 (SD 0.29), which was significantly better than the older age group (&ges;=55 years) of 0.82 (SD 0.40) (Mann-Whitney U test, p = 0.029). Conclusions: PDT using the predetermined treatment protocol has achieved similar visual outcomes in the Chinese population as in white people with subfoveal myopic CNV over a 2 year study period. The complete cessation of CNV leakage can be accomplished, on average, with fewer PDT retreatments than reported in the VIP study. The disparity may be due to ethnic differences in these two populations. [ABSTRACT FROM AUTHOR]

Presents letters to the editor concerning medical issues. Thoughts on taking responsibility for medical errors; Global campaign to eradicate malaria; Opioids used in the treatment of chronic non-malignant pain; Others.

Conclusion: Irrespective of size at birth, low weight gain during infancy is associated with increased risk of coronary heart disease. After age 1 year, rapid weight gain is associated with further increase in risk, but only among boys who were thin at birth. In these boys the adverse effects of rapid weight gain on later coronary heart disease are already apparent at age 3years. Improvements in fetal, infant, and child growth could lead to substantial reductions in the incidence of coronary heart disease. [ABSTRACT FROM AUTHOR]

Presents information on a study which examined whether catch-up growth during childhood modifies the increased risk of death from coronary heart disease that is associated with reduced intrauterine growth. Subjects and methods; Results and discussion; Conclusions.

The article comments on the 1906 landmark paper of Eduard Zirm, the first doctor who successfully performed a full-thickness corneal transplant. A case report was presented, describing the methods and procedures used in the corneal transplant, as well as the quality of the cornea and the tissue donated by a young boy. Also, Zirm mentioned the other conduct of operation which was important to the successful outcome besides meticulous asepsis and general anesthesia.

The article reports that scleral buckling is still the most common procedure to repair a rhematogenous retinal detachment. Acute or chronic infection of scleral explant is rare but well recognized serious postoperative complication threatening the eye and jeopardizing the retinal attachment and visual outcome. They may present acutely as painful red eye with purulent discharge or chronically with extrusion of the explants. The reported incidence varies between 0.5 percent and 5.6 percent. Surgical technique, different synthetic materials of scleral explants, duration of surgery, size, and position of buckle affect the rate of infection.

Severe acute respiratory syndrome (SARS) is a highly contagious potentially lethal disease. The main route of transmission is by respiratory droplets, though the virus has also been isolated in stool and urine. Tears, being one of the body fluids, may potentially harbor the coronavirus. The presence of viruses in these body fluids may affect precaution practices and sites of sampling for diagnostic tests. A prospective interventional case series study was conducted on the identification of the SARS-CoV virus in tear secretions and conjunctival cells of patients with confirmed SARS.

Background Tuberculosis clusters in families may be due to increased household exposure, shared genetic factors, or both. Household contact studies are useful to control exposure because socioeconomic and environmental conditions are similar to all subjects, allowing the evaluation of the contribution of relatedness to disease development. Methods In this study, the familial aggregation of tuberculosis using relatedness and a specific inherited marker (HLA-DRB1) was evaluated. Fifty families, which had at least two cases of tuberculosis diagnosed within the past 5 years, were selected from a cohort of tuberculosis carried out in Recife, Brazil. The first case diagnosed was considered to be a primary case. The secondary attack rate of tuberculosis in household contacts was estimated according to the degree of relatedness. The relative risk of having tuberculosis based on the degree of relatedness household and the population attributable fraction to relatedness were also estimated. HLA-DRB1 typing and attributable etiologic/preventive fractions were calculated among sick and healthy household contacts. Results Compared to unrelated contacts, the relative risk for tuberculosis adjusted for age was 1.38 (95% CI 0.86 to 2.21). Relatedness contributed 23% to the development of tuberculosis at the population levels. The HLA-DRB1*04 allele group (OR=2.44; p=0.0324; etiologic fraction=0.15) was overrepresented and the DRB1*15 allele group (OR=0.48; p=0.0488; protective fraction=0.19) was underrepresented among household contacts exhibiting tuberculosis. The presence of DRB1 shared alleles between primary cases and their contacts was a risk factor for tuberculosis (p=0.0281). Conclusion This household contact model together with the utilisation of two genetic variables permitted the evaluation of genetic factors contributing towards tuberculosis development. [ABSTRACT FROM AUTHOR]

Background/aims Diagnosis of rejection in the mouse model of corneal transplantation is based on subjective judgement of loss of graft transparency. The aims of this study were to (1) evaluate a pachymetry technique to measure changes in mouse corneal thickness and (2) correlate increases in transplant thickness with clinical and histological features of rejection. Methods Orthotopic corneal allografts (C57BL/6 strain donor) and syngeneic grafts were performed in A/J mice. Graft transparency was graded and corneal thickness measured by pachymetry on alternate days. Transverse sections of donor cornea excised from eyes representative of clinical opacity grades 1-4 were prepared, photographed, graft section thickness measured and stromal graft-infiltrating cells counted. Intraobserver and interobserver variations in pachymetry were statistically tested. Results Graft thickness, as measured by pachymetry, increased with each clinical opacity grade. Thickness for opacity grades 0, 1 and 2 was less than 300 μm in all recipients. Graft thickness for grades 3 and 4 was greater than 300 μm in all cases. For measurements up to 400 μm, there was a good correlation between thickness as measured by in vivo pachymetry and in histopathological sections. The mean interobserver bias was -11.35 .μm, while the mean intraobserver bias was +3.96 μm. Stromal cellularity increased with increasing corneal thickness up to approximately 300 μm. Conclusion In vivo graft pachymetry provides a new and reliable way to objectively diagnose rejection in the mouse model of corneal transplantation. [ABSTRACT FROM AUTHOR]

Objectives: To assess whether serial measurements of childhood body mass index (BMI) give clinically useful predictions of the risk of developing adult metabolic syndrome and impaired glucose tolerance or type 2 diabetes. Design/setting: Follow-up of a community-based birth cohort in Delhi, India. Participants: 1492 men and women aged 26-32 years whose BMI was recorded 6-monthly throughout childhood. Main outcome measures: The predictive value of childhood BMI for adult metabolic syndrome and impaired glucose tolerance (IGT) and diabetes mellitus. Results: 25% of subjects had metabolic syndrome and 15% had IGT/diabetes mellitus. Both outcomes were associated with greater childhood BMI gain (metabolic syndrome: OR 1.63 (95% CI 1.44 to 1.85); IGT/diabetes mellitus: 1.39 (1.20 to 1.60) per unit increase in within-cohort BMI SD score between 5 and 14 years). The best predictions of adult disease were obtained using a combined test comprising (i) any increase in BMI SD score between 5 and 14 years and (ii) a BMI SD score >0 at 14 years (metabolic syndrome: sensitivity 45%, specificity 78%; IGT/diabetes mellitus: 37%, 73%). Likelihood ratios were low (metabolic syndrome: 1.4-2.0; IGT/diabetes mellitus: 1.2-1.4). A single high BMI measurement at 14 years (overweight or obese, according to International Obesity Task Force criteria) was highly specific but insensitive (metabolic syndrome: sensitivity 7%, specificity 97%; IGT/diabetes mellitus: 8%, 97%). Charts for plotting BMI SD scores through childhood were produced. Conclusions: Serial measurements of childhood BMI give useful predictions of adult risk and could guide advice to children and parents on preventing later disease. [ABSTRACT FROM AUTHOR]