5†Tear proteins in premature babies at risk of retinopathy of prematurity.

This feasibility study aimed to investigate the feasibility of collecting and analysing tear proteins from preterm infants at risk of retinopathy of prematurity (ROP). Additionally, we sought to identify any tear proteins which might be implicated in the pathophysiology of ROP.Eligible infants were those undergoing ROP screening without other ocular pathology. Tear samples were obtained by Schirmer's test strips coincident with routine ROP screening. Mass spectrometry was used for proteomic analysis. All participants' parents gave written, informed consent.Samples were collected from 12 infants, including two sets of twins. Gestation ranged from 25+6 to 31+1 weeks. Median postnatal age at sampling was 30.5 days (range 19 to 66). One infant developed self-limiting ROP. An adequate sample for protein analysis was obtained from each infant. 701 proteins were identified; 261 proteins identified in the majority of tear samples, including several common tear proteins, were used for analyses.Increased risk of ROP as determined by G-ROP prediction criteria was associated with an increase in lactate dehydrogenase B (LDH-B) chain protein in tears. Older, more mature infants demonstrated increased concentration of immunoglobulin complexes within their tear samples and two sets of twins in the cohort showed exceptionally similar proteomes, supporting validity of the analysis.Tear sampling by Schirmer test strips and subsequent proteomic analysis in preterm infants is feasible. A larger study is required to investigate the potential use of tear proteomics in early identification of ROP.

2†Pathways to detection of non-infectious childhood uveitis in the UK: findings from the UNICORN cohort study.

INTRODUCTION: Prompt detection of childhood uveitis is key to minimising negative impact. From an internationally unique inception cohort, we report pathways to disease detection.UNICORNS is a national childhood non-infectious uveitis study with longitudinal collection of a standardised clinical dataset and patient reported outcomes. Descriptive analysis of baseline characteristics are reported.Amongst 150 recruited children (51% female, 31% non-white ethnicity) age at detection ranged from 2-18yrs (median 10). In 69%, uveitis was diagnosed following onset of symptoms: time from first symptoms to uveitis detection ranged from 0-739days (median 7days), with longer time to detection for those presenting initially to their general practitioner. Non symptomatic children were detected through JIA/other disease surveillance (16%), routine optometry review (5%) or child visual health screening (1%). Commonest underlying diagnoses at uveitis detection were JIA (17%), TINU (9%, higher than pre-pandemic reported UK disease frequency) and sarcoid (1%). 60% had no known systemic disease at uveitis detection. At disease detection, in at least one eye: 34% had structural complications (associated with greater time to detection - 17 days versus 4 days for uncomplicated presentation).The larger relative proportions of children with non-JIA uveitis reported here increase the importance of improving awareness of childhood uveitis amongst the wider clinical communities. There is scope for improvement of pathways to detection. Forthcoming analysis on the full cohort (251 recruited to date across 33 hospitals and 4 nations) will provide nationally representative data on management and the determinants of visual and broader developmental/well-being outcomes.

FAB: First UK feasibility trial of a future randomised controlled trial of Family focused treatment for Adolescents with Bipolar disorder.

BACKGROUND: This first mixed-methods UK trial examined the feasibility and acceptability of a future definitive randomised controlled trial (RCT) to evaluate whether Family Focussed Treatment for Adolescents with Bipolar Disorder (FFT-A) UK version can improve family functioning and well-being as part of the management of Paediatric Bipolar Disorder (PBD). METHOD: The trial used a randomised, parallel group, non-blinded design where participants received FFT-A UK (16 sessions over 6 months) immediately or after 12 months (delayed arm). Measures of family functioning, well-being and quality of life of the young person and the main carer (most commonly a parent) were completed at baseline, 6 and 12-months in both arms. Primary outcome measures included rates of eligibility, consent and retention along with estimates of variability in the measures and assessment of the intervention delivery. Qualitative interviews allowed assessment of participants' views about FFT-A and the trial processes. RESULTS: Twenty-seven of 36 young persons with PBD and their families consented; of these, 14 families were randomised to the immediate and 13 to the delayed arm. Two families from the immediate arm withdrew consent and discontinued participation. Quantitative measures were completed by 22 families (88%) at 6-months and 21 families (84%) at 12-months. Qualitative interviews were conducted with 30 participants (9 young people, 15 parents and 6 other family members). Nine families attended 3 post-trial focus groups. CONCLUSION: It was feasible to recruit and retain to this trial. The results highlighted that trial design and measures were acceptable to participants. A benefit in family relationships was reported by participants which they attributed to the intervention in qualitative interviews. Families recommended that future modifications include definitive trial(s) recruiting participants in the age range 15-25 years as it felt this was the age range with maximum need. Trial registration ISRCTN, ISRCTN59769322. Registered 20 January 2014, http://www.isrctn.com/ISRCTN59769322.

Value of ultrasound shear wave elastography in the diagnosis of adenomyosis.

BACKGROUND: The aim of the study was to assess the accuracy of ultrasound shear wave elastography in the diagnosis of adenomyosis. METHODS: One hundred and fifty three patients were examined. Ninety-seven patients were with suspected adenomyosis and 56 patients were with unremarkable myometrium. Adenomyosis was confirmed in 39 cases (A subgroup) and excluded in 14 cases (B subgroup) in the main group based on morphological examination. All patients underwent ultrasound examination using an Aixplorer (Supersonic Imagine, France) scanner with application of shear wave elastography during transvaginal scanning. Retrospective analysis of the elastography criteria against the findings from morphological/histological examination was performed. RESULTS: The following values of Young's modulus were found in subgroup A (adenomyosis): Emean - 72.7 (22.6-274.2) kPa (median, 5-95th percentiles), Emax - 94.8 (29.3-300.0) kPa, SD - 9.9 (2.6-26.3) kPa; in subgroup B (non adenomyosis) - 28.3 (12.7-59.5) kPa, 33.6 (16.0-80.8) kPa, 3.0 (1.4-15.6) kPa; in the control group - 24.4 (17.9-32.4) kPa, 29.8 (21.6-40.8) kPa, 2.3 (1.3-6.1) kPa, respectively (P < 0.05 for all comparison with subgroup В and the control group). The Emean cut-off value for adenomyosis diagnosis was 34.6 kPa. The sensitivity, specificity, positive predictive value, negative predictive value and area under curve (AUC) were 89.7%, 92.9%, 97.2%, 76.5% and 0.908. The Emax cut-off value was 45.4 kPa (89.7%, 92.9%, 97.2%, 76.5% and 0.907, respectively). CONCLUSION: This study showed a significant increase of the myometrial stiffness estimated with shear wave elastography use in patients with adenomyosis.

The phosphoprotein genes of measles viruses from subacute sclerosing panencephalitis cases encode functional as well as non-functional proteins and display reduced editing.

Products expressed from the second (P/V/C) gene are important in replication and abrogating innate immune responses during acute measles virus (MV) infection. Thirteen clone sets were derived from the P/V/C genes of measles virus (MV) RNA extracted from brains of a unique collection of seven cases of subacute sclerosing panencephalitis (SSPE) caused by persistent MV in the central nervous system (CNS). Whether these functions are fully maintained when MV replicates in the CNS has not been previously determined. Co-transcriptional editing of the P mRNAs by non-template insertion of guanine (G) nucleotides, which generates mRNAs encoding the viral V protein, occurs much less frequently (9%) in the SSPE derived samples than during the acute infection (30-50%). Thus it is likely that less V protein, which is involved in combatting the innate immune response, is produced. The P genes in MV from SSPE cases were not altered by biased hypermutation but exhibited a high degree of variation within each case. Most but not all SSPE derived phospho-(P) proteins were functional in mini genome replication/transcription assays. An eight amino acid truncation of the carboxyl-terminus made the P protein non-functional while the insertion of an additional glycine residue by insertion of G nucleotides at the editing site had no effect on protein function.

Prediction of outcome of early ER+ breast cancer is improved using a biomarker panel, which includes Ki-67 and p53.

BACKGROUND: The aim of this study is to determine whether immunohistochemical (IHC) assessment of Ki67 and p53 improves prognostication of oestrogen receptor-positive (ER+) breast cancer after breast-conserving therapy (BCT). In all, 498 patients with invasive breast cancer from a randomised trial of BCT with or without tumour bed radiation boost were assessed using IHC. METHODS: The ER+ tumours were classified as 'luminal A' (LA): ER+ and/or PR+, Ki-67 low, p53-, HER2- or 'luminal B' (LB): ER+ and/or PR+and/or Ki-67 high and/or p53+ and/or HER2+. Kaplan-Meier and Cox proportional hazards methodology were used to ascertain relationships to ispilateral breast tumour recurrence (IBTR), locoregional recurrence (LRR), distant metastasis-free survival (DMFS) and breast cancer-specific survival (BCSS). RESULTS: In all, 73 patients previously LA were re-classified as LB: a greater than four-fold increase (4.6-19.3%) compared with ER, PR, HER2 alone. In multivariate analysis, the LB signature independently predicted LRR (hazard ratio (HR) 3.612, 95% CI 1.555-8.340, P=0.003), DMFS (HR 3.023, 95% CI 1.501-6.087, P=0.002) and BCSS (HR 3.617, 95% CI 1.629-8.031, P=0.002) but not IBTR. CONCLUSION: The prognostic evaluation of ER+ breast cancer is improved using a marker panel, which includes Ki-67 and p53. This may help better define a group of poor prognosis ER+ patients with a greater probability of failure with endocrine therapy.

Identification of PUMA as an estrogen target gene that mediates the apoptotic response to tamoxifen in human breast cancer cells and predicts patient outcome and tamoxifen responsiveness in breast cancer.

Recognition of the pivotal role of estrogen in the aetiology of breast cancer has led to the development of antiestrogens (AE), such as tamoxifen (TAM) as effective therapies for the treatment and prevention of this disease. However, despite their widespread clinical efficacy, response to AEs is often short-lived, and acquired or innate therapeutic resistance remains a major obstacle in the successful treatment of breast cancer. Thus, delineating the intracellular pathways that mediate the cellular response to estrogen could potentially lead to new, more effective approaches to the treatment of breast cancer, particularly endocrine-resistant disease. Here, we have identified the BCL-2 homology 3 (BH3)-only, pro-apoptotic regulator, PUMA (p53 upregulated modulator of apoptosis) as an estrogen target gene that is acutely downregulated in response to estrogen in breast cancer cell lines, independently of their p53 status. PUMA is transcriptionally upregulated following treatment with TAM, and knock down of PUMA expression in these cells attenuates the apoptotic response to TAM. Furthermore, low PUMA expression in breast carcinomas is significantly associated with breast cancer-specific death (P=0.0014 and P=0.0115, for mRNA and protein, respectively), and worse outcome in TAM-treated patients (mRNA, P=1.49e-05). These findings suggest that the dysregulation of apoptotic signaling pathways such as those executed through PUMA, can significantly impact on both the progression and therapeutic responsiveness of breast cancer. Moreover, they provide a convincing rationale for exploring new therapeutic approaches involving endocrine and non-endocrine therapies that target apoptotic pathways as an effective strategy for tackling endocrine refractory disease.

Cyclin D1b protein expression in breast cancer is independent of cyclin D1a and associated with poor disease outcome.

Aberrant expression of cyclin D1 protein is a common feature of breast cancer. However, the CCND1 gene encodes two gene products, cyclin D1a and cyclin D1b, which have discrete mechanisms of regulation and impact on cell behavior. A polymorphism at nucleotide 870 in the CCND1 gene, rs603965, influences the relative production of the encoded proteins and can impart increased risk for tumor development. Here, the impact of both the G/A870 polymorphism and cyclin D1b protein production on breast cancer risk, disease phenotype and patient outcome was analysed. In a large multiethnic case-control study, the G/A870 polymorphism conferred no significant risk for breast cancer overall or by stage or estrogen receptor (ER) status. However, the cyclin D1b protein was found to be upregulated in breast cancer, independent of cyclin D1a levels, and exhibited heterogeneous levels in breast cancer specimens. High cyclin D1a expression inversely correlated with the Ki67 proliferation marker and was not associated with clinical outcome. In contrast, elevated cyclin D1b expression was independently associated with adverse outcomes, including recurrence, distant metastasis and decreased survival. Interestingly, cyclin D1b was particularly associated with poor outcome in the context of ER-negative breast cancer. Thus, specific cyclin D1 isoforms are associated with discrete forms of breast cancer and high cyclin D1b protein levels hold prognostic potential.

The key hypoxia regulated gene CAIX is upregulated in basal-like breast tumours and is associated with resistance to chemotherapy.

Basal-like tumours account for 15% of invasive breast carcinomas and are associated with a poorer prognosis and resistance to therapy. We hypothesised that this aggressive phenotype is because of an intrinsically elevated hypoxic response. Microarrayed tumours from 188 patients were stained for hypoxia-inducible factor (HIF)-1alpha, prolyl hydroxylase (PHD)1, PHD2, PHD3 and factor inhibiting HIF (FIH)-1, and carbonic anhydrase (CA) IX stained in 456 breast tumours. Tumour subtypes were correlated with standard clincopathological parameters as well as hypoxic markers. Out of 456 tumours 62 (14%) tumours were basal-like. These tumours were positively correlated with high tumour grade (P<0.001) and were associated with a significantly worse disease-free survival compared with luminal tumours (P<0.001). Fifty percent of basal-like tumours expressed HIF-1alpha, and more than half expressed at least one of the PHD enzymes and FIH-1. Basal-like tumours were nine times more likely to be associated with CAIX expression (P<0.001) in a multivariate analysis. Carbonic anhydrase IX expression was positively correlated with tumour size (P=0.005), tumour grade (P<0.001) and oestrogen receptor (ER) negativity (P<0.001). Patients with any CAIX-positive breast tumour phenotype and in the basal tumour group had a significantly worse prognosis than CAIX-negative tumours when treated with chemotherapy (P<0.001 and P=0.03, respectively). The association between basal phenotype and CAIX suggests that the more aggressive behaviour of these tumours is partly due to an enhanced hypoxic response. Further, the association with chemoresistance in CAIX-positive breast tumours and basal-like tumours in particular raises the possibility that targeted therapy against HIF pathway or downstream genes such as CAs may be an approach to investigate for these patients.

BAG-1 predicts patient outcome and tamoxifen responsiveness in ER-positive invasive ductal carcinoma of the breast.

BAG-1 (bcl-2-associated athanogene) enhances oestrogen receptor (ER) function and may influence outcome and response to endocrine therapy in breast cancer. We determined relationships between BAG-1 expression, molecular phenotype, response to tamoxifen therapy and outcome in a cohort of breast cancer patients and its influence on tamoxifen sensitivity in MCF-7 breast cancer cells in vitro. Publically available gene expression data sets were analysed to identify relationships between BAG-1 mRNA expression and patient outcome. BAG-1 protein expression was assessed using immunohistochemistry in 292 patients with invasive ductal carcinoma and correlated with clinicopathological variables, therapeutic response and disease outcome. BAG-1-overexpressing MCF-7 cells were treated with antioestrogens to assess its effects on cell proliferation. Gene expression data demonstrated a consistent association between high BAG-1 mRNA and improved survival. In ER+ cancer (n=189), a high nuclear BAG-1 expression independently predicted improved outcome for local recurrence (P=0.0464), distant metastases (P=0.0435), death from breast cancer (P=0.009, hazards ratio 0.29, 95% CI: 0.114-0.735) and improved outcome in tamoxifen-treated patients (n=107; P=0.0191). BAG-1 overexpression in MCF-7 cells augmented antioestrogen-induced growth arrest. A high BAG-1 expression predicts improved patient outcome in ER+ breast carcinoma. This may reflect both a better definition of the hormone-responsive phenotype and a concurrent increased sensitivity to tamoxifen.

Supraclavicular radiotherapy must be limited laterally by the coracoid to avoid significant adjuvant breast nodal radiotherapy lymphoedema risk.

This cross-sectional study aimed to investigate the effect of supraclavicular fossa (SCF) radiotherapy volumes as well as patient characteristics and nodal pathology on the development of lymphoedema. Ninety-one women who had received SCF nodal radiotherapy after axillary dissection were evaluated. Lymphoedema was defined by two measurements: limb volume difference 200 mL, or circumference difference 10 cm proximal or distal to the olecranon>2 cm. On univariate analysis, the addition of axillary to SCF radiotherapy, increasing width of the SCF field, increasing age, presence of extracapsular extension of nodal involvement and use of hormone treatment was associated with lymphoedema by either one or both definitions. For both definitions of lymphoedema, on multivariate analysis, increasing nodal radiotherapy volume remained significant (P=0.02 to 0.007), as did increased age (P=0.05 to 0.001). We conclude that conventionally fractionated SCF radiotherapy limited laterally by the coracoid process has a lymphoedema risk similar to that expected from axillary dissection alone and a lower risk than wider SCF fields with or without an axillary boost.

Myopericytoma: a unifying term for a spectrum of tumours that show overlapping features with myofibroma. A review of 14 cases.

BACKGROUND: Myopericytoma (MPC) is a recently proposed term to describe a group of tumours that originate from perivascular myoid cells and show a range of histological growth patterns. Only a small number of series describing MPC have been reported. MPC is frequently misdiagnosed as a sarcoma. AIMS: To document the clinical and histopathological findings of a series of MPCs, to describe the range of growth patterns and morphological spectrum, and to compare MPC with myofibroma (MF). PATIENTS/METHODS: Fourteen patients with features of MPC and/or MF were identified from the archival files of the department of anatomical pathology, Royal Prince Alfred Hospital, Sydney, Australia. RESULTS: There were six female and eight male patients. The mean and median patient ages were 37 and 35.5 years, respectively. The tumours were located in the skin, subcutis, or superficial soft tissues of the distal extremities (13 patients) or the head and neck region (one patient), and showed a spectrum of morphological appearances. They were divided into two groups based upon the predominant growth pattern corresponding to MPC (seven cases) and MF (seven cases). The feature most suggestive of MPC was the presence of a concentric perivascular arrangement of plump spindle shaped cells. The presence of a zonation/biphasic appearance was most characteristic of MF. CONCLUSIONS: MPC exhibits a spectrum of growth patterns that overlap with MF. Tumours can be designated as MPC or MF depending on the predominant growth pattern.

Gene expression profiling in breast cancer: towards individualising patient management.

Breast cancer is a complex and clinically heterogeneous disease. The increase in knowledge of breast cancer biology has led to a number of clinical advances in the treatment of breast cancer, most notably the implementation of widespread mammography screening and advances in adjuvant treatment of early-stage disease. In the last 20 years, arrays of potential prognostic and/or predictive markers of breast cancer have been analysed. However, relatively few have proven to be clinically useful. To date, the only widely accepted markers for routine use in breast cancer are the oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor, HER-2 (c-erbB2/neu). Expression microarray technology and laser capture microdissection have now been employed to further our understanding of the molecular pathogenesis of breast cancer. Recently reported advances in array technology and RNA amplification methods are having a considerable impact in this field, allowing the analysis of pre-malignant and pre-invasive lesions. A number of studies have identified prognostic and predictive gene 'signatures', whose prediction of disease outcome and response to treatment is superior to conventional prognostic indicators. Despite major technological advances, a number of confounding issues remain concerning the potential clinical utility of gene expression profiling, including differences in study design, patient selection, array technology, chemistry, and methods of analysis. It seems likely, however, that following careful 'hypothesis driven' validation studies and clinical trials, expression profiling will be applied in the future to identify patient-specific disease profiles and provide rationale for individualised treatment. This review focuses on the current use and future potential of microarray profiling in breast cancer.

Extragenital mullerian adenosarcoma with sarcomatous overgrowth arising in an endometriotic cyst in the pouch of Douglas.

Mullerian adenosarcoma is a neoplasm composed of benign mullerian epithelium and a sarcomatous stroma. This tumor classically occurs in the endometrium of postmenopausal women and less frequently in the extrauterine genital tract. Rare cases of extragenital adenosarcoma have been reported. We present the case of a 23-year-old female who presented with an extragenital adenosarcoma arising in an endometriotic cyst in the pouch of Douglas. The patient was treated with local excision, chemotherapy and radiotherapy. At 2 years follow-up she was disease-free. The literature on extragenital adenosarcoma is reviewed. These tumors are clinically more aggressive than their uterine counterparts. Surgical excision is the initial treatment modality for these patients. Little information is available regarding the efficacy of adjuvant chemotherapy or radiotherapy. This is an area that requires further study.

Do oxidized fatty acids activate coagulation factor VII during post-prandial lipemia in women?

Factor VII is activated to VIIa within hours after dietary fat, irrespective of its fatty acid composition. Edible oils contain oxidized material (hydroxy fatty acids, HOFA). Twenty-five fasting women, aged 38 (10) years, consumed 30 g walnut oil containing 26 (6) mg HOFA. Blood was collected 2-hourly to measure plasma triglycerides and plasma lipid HOFA by gas chromatography/mass spectrometry. VII and sTF-dependent VIIa were quantified at 0, 6 and 24 h. Increased plasma triglycerides and HOFA (areas under the curve 0-8 h, AUC) were related r = 0.83, p < 0.001. VIIa increased from 2.6 (1.4) to 4.2 (1.9) ng/mL at 6 h (p < 0.001). Plasma VII remained constant. VIIa (6 h) was related to plasma triglycerides- and HOFA-AUC: r = 0.38 and 0.53, respectively (both p < 0.05). Plasma VIIa was also related to body weight, fasting triglycerides, HOFA and VII. Only HOFA-AUC and body weight related to VIIa (6 h) in stepwise regression analysis (p = 0.007 and 0.038, respectively). Oxidized, not normal, fat activates VII and could increase coronary risk in humans.

Selenium supplementation acting through the induction of thioredoxin reductase and glutathione peroxidase protects the human endothelial cell line EAhy926 from damage by lipid hydroperoxides.

The human endothelial cell line EAhy926 was used to determine the importance of selenium in preventing oxidative damage induced by tert-butyl hydroperoxide (tert-BuOOH) or oxidised low density lipoprotein (LDLox). In cells grown in a low selenium medium, tert-BuOOH and LDLox killed cells in a dose-dependent manner. At 555 mg/l LDLox or 300 microM tert-BuOOH, >80% of cells were killed after 20 h. No significant cell kill was achieved by these agents if cells were pre-incubated for 48 h with 40 nM sodium selenite, a concentration that maximally induced the activities of cytoplasmic glutathione peroxidase (cyGPX; 5.1-fold), phospholipid hydroperoxide glutathione peroxidase (PHGPX;1.9-fold) and thioredoxin reductase (TR; 3.1-fold). Selenium-deficient cells pre-treated with 1 microM gold thioglucose (GTG) (a concentration that inhibited 25% of TR activity but had no inhibitory effect on cyGPX or PHGPX activity) were significantly (P<0.05) more susceptible to tert-BuOOH toxicity (LC(50) 110 microM) than selenium-deficient cells (LC(50) 175 microM). This was also the case for LDLox. In contrast, cells pre-treated with 40 nM selenite prior to exposure to GTG were significantly more resistant to damage from tert-BuOOH and LDLox than Se-deficient cells. Treatment with GTG or selenite had no significant effect on intracellular total glutathione concentrations. These results suggest that selenium supplementation, acting through induction of TR and GPX, has the potential to protect the human endothelium from oxidative damage.

Significance and assessment of margin status in ductal carcinoma in situ of the breast.

This article reviews practical and theoretical aspects of margin assessment for surgically excised ductal carcinoma in situ of the breast. Different methods of assessing surgical margins are discussed, including selected tangential sections, the margin shaving, and cavity peel methods. Criteria for margin adequacy and the relevance of margin status in the selection of cases for breast conservation are discussed in the context of other important risk factors for local failure.

Mucinous differentiation in colonic adenocarcinoma is associated with a reduction in tumour-infiltrating lymphocytes.

AIMS: The aim of this study was to examine the density of tumour-infiltrating lymphocytes (TILs) in colorectal carcinomas showing mucinous differentiation. METHODS: We examined 33 adenocarcinomas showing variable mucinous differentiation and compared the density of TILs with that of 65 adenocarcinomas of no special type (NOS) showing no mucinous differentiation. RESULTS: Mucinous differentiation is associated with a significantly lower density of TILs compared to adenocarcinoma NOS (P=0.0016; chi-squared test with continuity correction). This reduction in TILs is present also in adjacent foci of adenocarcinoma NOS within mucinous tumours. CONCLUSIONS: There is a reduction in the number of TILs in all areas of colorectal adenocarcinomas that show mucinous differentiation, which may help explain the increased biological aggressiveness associated with this pattern of differentiation.

Toward elimination of Haemophilus influenzae type B carriage and disease among high-risk American Indian children.

OBJECTIVES: This report describes the epidemiology of Haemophilus influenzae type b (Hib) invasive disease and oropharyngeal colonization among Navajo and White Mountain Apache children younger than 7 years in an era of widespread immunization. METHODS: We conducted active surveillance for invasive H influenzae disease from 1992 to 1999 and an oropharyngeal carriage study from 1997 to 1999. The predominant vaccine used was PedvaxHib. RESULTS: The average annual incidence of invasive Hib disease among children younger than 24 months was 22 cases per 100,000. Of 381 children younger than 7 years, only 1 (0.3%; 95% confidence interval = 0.0%, 1.3%) was colonized with Hib; 370 (97%) had received 2 or more doses of Hib conjugate vaccine. CONCLUSIONS: Among Navajo and White Mountain Apache children, Hib conjugate vaccines have led to a sustained reduction in invasive Hib disease and a reduction in oropharyngeal Hib carriage. The disease incidence among children younger than 24 months remains 20 times higher than in the general US population. Hib elimination will require additional characterization of colonization and disease in these high-risk populations.

Sta-Peg arthroereisis for treatment of the planovalgus foot in cerebral palsy.

The Sta-Peg procedure is most effective in the non-rigid foot in which reasonable muscle balance can be attained. Where such balance cannot be attained or where rigid deformity exists, this procedure will not solve the problem and should not be used. The authors want to emphasize that this study pertains to the use of Sta-Peg in the valgus foot caused by cerebral palsy. The procedure is rarely needed in the flexible flatfoot of a normal child.