Prevalence of Glaucoma Following Paediatric Cataract Surgery in an Australian Tertiary Referral Centre.

Purpose: Secondary glaucoma following childhood cataract surgery remains the most common complication in the paediatric population. This study aimed to determine the incidence, time to progression and risk factors associated with the development of secondary glaucoma following childhood cataract surgery in a paediatric population. Outcome measures were the detection of secondary glaucoma, postoperative time frame to development of glaucoma and risk factors in its development. Patients and Methods: A retrospective case series was conducted between 2003 and 2017 at a tertiary children's hospital in Sydney. The patient population included those 16 years or less of age who underwent congenital cataract extraction, with or without an intraocular lens implantation and who had been followed up for a minimum of six months following surgery. Patients were excluded if they had cataract aetiology other than congenital idiopathic cataract. Multivariate Cox Regression analysis was used to determine relevant risk factors. Results: A total of 320 eyes in 216 patients were included in the study. Secondary glaucoma developed in 11.9% of eyes. In those that developed secondary glaucoma, the average time to onset from surgery was 3.2 years (median 2.75 years). The mean age of diagnosis of secondary glaucoma was 4.58 years (median 3.5 years, range 2.5 months to 13.23 years). Microcornea was the only adverse characteristic significantly associated with an increased risk of secondary glaucoma (HR 6.30, p 0.003). Conclusion: Despite modern surgical techniques, glaucoma remains a significant long-term sequela in children following cataract surgery.

Beam dynamic study of a Ka-band microwave undulator and its potential drive sources.

Microwave undulators (MUs) have great potential to be an alternative solution to permanent magnet undulators in a free electron laser (FEL) when shorter undulator periods are required. In this paper, the factors that affect the choice of the high-power drive sources were studied via a Ka-band cavity-type MU with a corrugated waveguide proposed for the CompactLight X-ray FEL. They include the technology of the high-power vacuum electronic devices, the quality factor of the MU cavity that was demonstrated by prototyping a short section of the MU structure, and the beam dynamic study of the electrons' trajectories inside the MU. It showed that at high beam energy, a high-power oscillator is feasible to be used as the drive source. At low beam energy, the maximum transverse drift distance becomes larger therefore an amplifier has to be used to minimize the drift distance of the electrons by controlling the injection phase.

Risk stratification after recurrence of human papillomavirus (HPV)-related and non-HPV-related oropharyngeal cancer: Secondary analysis of NRG Oncology RTOG 0129 and 0522.

BACKGROUND: No risk-stratification strategies exist for patients with recurrent oropharyngeal cancer (OPC). METHODS: Retrospective analysis using data from prospective NRG Oncology clinical trials RTOG 0129 and 0522. Eligibility criteria included known p16 status and smoking history, and locoregional/distant recurrence. Overall survival (OS) was measured from date of recurrence. Recursive partitioning analysis was performed to produce mutually exclusive risk groups. RESULTS: Hundred and fifty-four patients were included with median follow-up after recurrence of 3.9 years (range 0.04-9.0). The most important factors influencing survival were p16 status and type of recurrence, followed by surgical salvage and smoking history (≤20 vs. >20 pack-years). Three significantly different risk groups were identified. Patients in the low-, intermediate-, and high-risk groups had 2-year OS after recurrence of 81.1% (95%CI 68.5-93.7), 50.2% (95%CI 36.0-64.5), and 20.8% (95%CI 10.5-31.1), respectively. CONCLUSION: Patient and tumor characteristics may be used to stratify patients into risk groups at the time of OPC recurrence.

"We don't have up to date knowledge about the disease" Practical challenges encountered in delivery of cervical cancer screening in Iraq.

This qualitative study aimed to explore the lived experience of medical doctors in delivering cervical cancer screening in a city in Iraq. METHODS: An applied grounded theory approach explored the reported experiences of doctors in the field. A purposive sample of 12 gynaecologists and one general practitioner (GP) working in two main hospitals participated: Semi-structured interviews took place from June to September 2015. Thematic coding of data was peer reviewed and included participant reading of transcripts and translations from Arabic to English. Theory generation involved synthesis of a prior literature review and interview findings. RESULTS: Gynaecologist and GP experiences showed overwhelming gaps in cervical cancer experience and screening. Iraqi women mainly presented for help with late-stage cancer. Practical barriers included cultural stigma, low priority for women's health needs, lack of knowledgeable leadership and perceived shortage of adequately trained staff. CONCLUSION: There is an urgent need for culturally appropriate cervical cancer prevention policies and strategies in Iraq, focused on evidence-based population-based cervical screening to identify and prevent advanced cervical cancer among women. Regional educational initiatives should be encouraged and primary healthcare systems supported to undertake screening.

Chemotherapy-induced genotoxic damage to bone marrow cells: long-term implications.

Mesenchymal stem/stromal cells (MSCs) within the bone marrow (BM) are vitally important in forming the micro-environment supporting haematopoiesis after myeloablative chemotherapy. MSCs are known to be damaged phenotypically and functionally by chemotherapy; however, to the best our knowledge, the persistence of genotoxic effects of chemotherapy on the BM micro-environment has not been studied. We therefore aimed to evaluate genotoxic effects of chemotherapy on the BM both in vitro and in vivo, using the comet and micronucleus assays, focussing on the persistence of DNA lesions that may contribute to complications in the patient. The MSC cell line (HS-5) and primary cord blood mononuclear cells (CBMNCs: a source of undamaged DNA) were exposed to the chemotherapeutic agent cyclophosphamide (CY) within a physiologically relevant in vitro model. CY treatment resulted in significant increases in CBMNC DNA damage at all time points tested (3-48 h exposure). Similarly, HS-5 cells exposed to CY exhibited significant increases in DNA damage as measured by the comet assay, with increased numbers of abnormal cells visible in the micronucleus assay. In addition, even 48 h after removal of 48-h CY treatment, DNA damage remains significantly increased in treated cells relative to controls. In patients treated with chemotherapy for haematological malignancy, highly significant increases in damaged DNA were seen in BM cells isolated from one individual 1 year after completion of therapy for acute leukaemia compared with pretreatment (P < 0.001). Similarly, two individuals treated 7 and 17 years previously with chemotherapy exhibited significant increases of damaged DNA in MSC compared with untreated age- and sex-matched controls (P < 0.05). Unlike haematopoietic cells, MSCs are not replaced following a stem cell transplant. Therefore, long-term damage to MSC may impact on engraftment of either allogeneic or autologous transplants. In addition, persistence of DNA lesions may lead to genetic instability, correlating with the significant number of chemotherapy-treated individuals who have therapy-related malignancies.

Integrative review of cervical cancer screening in Western Asian and Middle Eastern Arab countries.

Population-based screening programs have resulted in minimizing mortality and morbidity from cervical cancer. The aim of this integrative review was to explore the factors influencing access of women from Western Asian and Middle Eastern Arab countries to cervical cancer screening. A systematic search for studies conducted in Arab countries in those regions, and published in English between January 2002 and January 2017, was undertaken. Thirteen papers were selected and subjected to quality appraisal. A three step analysis was used, which involved a summary of the evidence, analysis of both quantitative and qualitative data, and integration of the results in narrative form. Few population-based cervical cancer screening programs had been implemented in the relevant countries, with low knowledge of, and perceptions about, cervical screening among Arab women, the majority of whom are Muslim. Factors affecting the uptake of cervical cancer screening practices were the absence of organized, systematic programs, low screening knowledge among women, healthcare professionals' attitudes toward screening, pain and embarrassment, stigma, and sociocultural beliefs. Policy changes are urgently needed to promote population-based screening programs. Future research should address the promotion of culturally-sensitive strategies to enable better access of Arab Muslim women to cervical cancer screening.

Photographic assessment of retinal hemorrhages in infant head injury: the Childhood Hemorrhagic Retinopathy Study.

BACKGROUND: Retinal hemorrhages (RH) in babies in the absence of severe trauma or a medical cause have been strongly associated with abusive head trauma (AHT). We examined the pattern of RH in accidental head injury and AHT objectively using widefield retinal imaging. METHODS: A total of 118 infants and children 1-36 months of age admitted with head injuries at two centers were included in this prospective, consecutive, comparative cohort study. Dilated fundus examination was performed with indirect ophthalmoscopy and widefield imaging. Designation of AHT was made using predetermined criteria independent of retinal findings. Retinal images were graded by two independent observers. RESULTS: There were 21 cases of AHT. RH were present in 14 cases (66%); macular retinoschisis or retinal folds, in 8 (38%). There were 86 cases of accidental head injuries, with RH present in 2 (2%); there were none with retinal folds or retinoschisis. In cases of head injury with intracranial hemorrhage, the positive likelihood ratio of AHT with RH was 5.7 (95% CI, 2.6-12.00) and negative likelihood ratio was 0.26 (95% CI, 0.11-0.62). A severe, panretinal pattern with multilayered hemorrhages was the most specific for AHT. CONCLUSIONS: Our imaging study confirmed that RH in infants with head injury have a high positive likelihood ratio for AHT. A severe hemorrhagic retinopathy, particularly in association with perimacular folds or macular retinoschisis, has the highest positive predictive value for AHT.

Malignant Hypertensive Retinopathy in an Infant with Mid-Aortic Occlusion.

Purpose. Case report describing an eight-month-old infant presenting with intermittent esotropia and irritability who was found to have malignant (grade 4) hypertensive retinopathy and mid-aortic syndrome. Methods. Visual acuity was 6/140 in the right eye and not recordable in the left eye. Blood pressure was as high as 230/120 mmHg. Fundoscopy revealed bilateral optic disc swelling, macular stars, and serous retinal detachment in the left eye, findings that are consistent with malignant (grade 4) hypertensive retinopathy. CT abdominal angiogram revealed a severe mid-aortic syndrome with occlusion of the abdominal aorta at T12. Results. The patient was treated with medical management of his hypertension, improving the subretinal exudate. Binocular visual acuity improved to 6/9.5 over 9 months. There was a persistent left relative afferent pupillary defect and moderate left esotropia. Conclusion. This is the first reported case of malignant hypertensive retinopathy in an infant with concomitant mid-aortic occlusion. The authors emphasize the need for an ophthalmological and pediatric examination in a child presenting with intermittent squint and irritability. The esotropia was found to be a false localizing sign of raised intracranial pressure secondary to the severe mid-aortic syndrome.

Advantage of Whole Exome Sequencing over Allele-Specific and Targeted Segment Sequencing in Detection of Novel TULP1 Mutation in Leber Congenital Amaurosis.

BACKGROUND: Leber congenital amaurosis (LCA) is a severe form of retinal dystrophy with marked underlying genetic heterogeneity. Until recently, allele-specific assays and Sanger sequencing of targeted segments were the only available approaches for attempted genetic diagnosis in this condition. A broader next-generation sequencing (NGS) strategy, such as whole exome sequencing, provides an improved molecular genetic diagnostic capacity for patients with these conditions. MATERIALS AND METHODS: In a child with LCA, an allele-specific assay analyzing 135 known LCA-causing variations, followed by targeted segment sequencing of 61 regions in 14 causative genes was performed. Subsequently, exome sequencing was undertaken in the proband, unaffected consanguineous parents and two unaffected siblings. Bioinformatic analysis used two independent pipelines, BWA-GATK and SOAP, followed by Annovar and SnpEff to annotate the variants. RESULTS: No disease-causing variants were found using the allele-specific or targeted segment Sanger sequencing assays. Analysis of variants in the exome sequence data revealed a novel homozygous nonsense mutation (c.1081C > T, p.Arg361*) in TULP1, a gene with roles in photoreceptor function where mutations were previously shown to cause LCA and retinitis pigmentosa. The identified homozygous variant was the top candidate using both bioinformatic pipelines. CONCLUSIONS: This study highlights the value of the broad sequencing strategy of exome sequencing for disease gene identification in LCA, over other existing methods. NGS is particularly beneficial in LCA where there are a large number of causative disease genes, few distinguishing clinical features for precise candidate disease gene selection, and few mutation hotspots in any of the known disease genes.

Grading system for retinal hemorrhages in abusive head trauma: clinical description and reliability study.

PURPOSE: There is currently no universally accepted grading system for describing retinal hemorrhages (RH) in abusive head trauma (AHT). The purpose of this study was to devise and evaluate a novel grading system and descriptive nomenclature for RH in AHT for clinical and research purposes. METHODS: A traumatic hemorrhagic retinopathy (THR) grading system was developed for assessing and quantitatively analyzing retinal findings in abusive head trauma. The criteria for the THR grade included the extent, spread, and morphology of RH. Extent was classified as region 1 (posterior pole) or region 2 (peripheral). Spread, based on number of retinal hemorrhages, was classified as mild (10 or fewer RH), moderate (more than 10 RH) and severe (more than half of involved regions covered by RH). Morphology was classified by its intraretinal or extraretinal involvement. Two independent graders calculated the THR grade from RetCam images of 38 eyes of 19 patients <3 years of age with retinal hemorrhages associated with head injury. Grading was performed on two separate occasions. Intra- and interobserver reliability was assessed with Spearman correlation coefficient (r) and intraclass correlation coefficient (ICC). RESULTS: There was a high level of intraobserver agreement across both assessments (97% agreement [Spearman r = 0.997; P < 0.0001] and 100% agreement [Spearman r = 1.0; P < 0.0000]). Intraclass correlation (ICC, 0.995; 95% CI, 0.991-0.997; P < 0.0001) confirmed a very high level of agreement overall. CONCLUSIONS: The traumatic hemorrhagic retinopathy grading system demonstrated excellent intraobserver and interobserver reliability. The nomenclature is easily understood and may be useful in medical records and medicolegal reports.

Microphthalmia, anophthalmia, and coloboma and associated ocular and systemic features: understanding the spectrum.

IMPORTANCE: Microphthalmia, anophthalmia, and coloboma form an interrelated spectrum of congenital eye abnormalities. OBJECTIVE: To document the ocular and systemic findings and inheritance patterns in patients with microphthalmia, anophthalmia, and coloboma disease to gain insight into the underlying developmental etiologies. DESIGN, SETTING, AND PARTICIPANTS: This retrospective consecutive case series was conducted at a tertiary referral center. Included in the study were 141 patients with microphthalmia, anophthalmia, and coloboma disease without a recognized syndromic etiology who attended the Westmead Children's Hospital, Sydney, from 1981-2012. EXPOSURE: Cases were grouped on the basis of the presence or absence of an optic fissure closure defect (OFCD); those with OFCD were further subdivided into microphthalmic and nonmicrophthalmic cases. Anophthalmic cases were considered as a separate group. MAIN OUTCOMES AND MEASURES: Associated ocular and systemic abnormalities and inheritance patterns were assessed. RESULTS: Of 141 cases, 61 (43%) were microphthalmic non-OFCD (NOFCD), 34 (24%) microphthalmic OFCD, 32 (23%) nonmicrophthalmic coloboma (OFCD), 9 (6%) anophthalmic, and 5 (4%) were unclassified. Sixty-three (45%) had bilateral disease. Eighty-four patients (60%) had an associated ocular abnormality; of these, cataract (P < .001) and posterior segment anomalies (P < .001) were most common in the NOFCD group. Forty-eight (34%) had an associated systemic abnormality, most commonly neurological, musculoskeletal and facial, urological and genital, or cardiac. Neurological abnormalities were most common in the anophthalmic group (P = .003), while urological abnormalities were particularly seen in the OFCD groups (P = .009). Familial cases were identified in both the OFCD and NOFCD groups, with a likely autosomal dominant inheritance pattern in 9 of 10 families. CONCLUSIONS AND RELEVANCE: This series indicated that the OFCD/NOFCD distinction may be useful in guiding evaluation for ocular and systemic associations, as well as the direction and analysis of genetic investigation.

Development of a novel, physiologically relevant cytotoxicity model: application to the study of chemotherapeutic damage to mesenchymal stromal cells.

There is an increasing need for development of physiologically relevant in-vitro models for testing toxicity, however determining toxic effects of agents which undergo extensive hepatic metabolism can be particularly challenging. If a source of such metabolic enzymes is inadequate within a model system, toxicity from prodrugs may be grossly underestimated. Conversely, the vast majority of agents are detoxified by the liver, consequently toxicity from such agents may be overestimated. In this study we describe the development of a novel in-vitro model, which could be adapted for any toxicology setting. The model utilises HepG2 liver spheroids as a source of metabolic enzymes, which have been shown to more closely resemble human liver than traditional monolayer cultures. A co-culture model has been developed enabling the effect of any metabolised agent on another cell type to be assessed. This has been optimised to enable the study of damaging effects of chemotherapy on mesenchymal stem cells (MSC), the supportive stem cells of the bone marrow. Several optimisation steps were undertaken, including determining optimal culture conditions, confirmation of hepatic P450 enzyme activity and ensuring physiologically relevant doses of chemotherapeutic agents were appropriate for use within the model. The developed model was subsequently validated using several chemotherapeutic agents, both prodrugs and active drugs, with resulting MSC damage closely resembling effects seen in patients following chemotherapy. Minimal modifications would enable this novel co-culture model to be utilised as a general toxicity model, contributing to the drive to reduce animal safety testing and enabling physiologically relevant in-vitro study.

Evaluation of a method allowing preservation of fresh lymph nodes for flow cytometric immunophenotyping.

BACKGROUND: Flow cytometric immunophenotyping (FCI) of lymph nodes (LN) requires fresh unfixed tissue, with analysis being carried out within few hours post surgery. This study evaluated a novel method for fresh LN preservation, in order to allow histomorphology-based FCI. METHODS: This study was carried out prospectively on 30 LN with suspected involvement by haematolymphoid neoplasms (HLN). FCI was performed on each fresh and post cryopreserved LN cell suspension. Percentage positivities (PP) and mean fluorescent intensities (MFI) were calculated on both preparations for a combination of T and B-lymphoid antigens together with viability. RESULTS: The cryopreservation method applied in this study did not affect significantly PP and had minor impact on MFI of the tested antigens. Overall, there was minimal decrease in PP and MFI on the cryopreserved cells when compared with fresh cells, for most antigens with only a mild increase in apoptotic cells. However, these changes were not diagnostically significant, since both reactive processes and HLN present within analyzed LN could be identified and differentiated. Viability was more than 75% for all cryopreserved LN composed of haematolymphoid cells. CONCLUSION: The method presented in this study confers the possibility of storing fresh LN biopsies for later FCI, thus allowing a morphology-based immunophenotypic approach. This would allow a more sensitive, specific, and cost-effective management of LN specimens, whilst maintaining the important benefits provided by FCI.

Alkylating chemotherapeutic agents cyclophosphamide and melphalan cause functional injury to human bone marrow-derived mesenchymal stem cells.

The adverse effects of melphalan and cyclophosphamide on hematopoietic stem cells are well-known; however, the effects on the mesenchymal stem cells (MSCs) residing in the bone marrow are less well characterised. Examining the effects of chemotherapeutic agents on patient MSCs in vivo is difficult due to variability in patients and differences in the drug combinations used, both of which could have implications on MSC function. As drugs are not commonly used as single agents during high-dose chemotherapy (HDC) regimens, there is a lack of data comparing the short- or long-term effects these drugs have on patients post treatment. To help address these problems, the effects of the alkylating chemotherapeutic agents cyclophosphamide and melphalan on human bone marrow MSCs were evaluated in vitro. Within this study, the exposure of MSCs to the chemotherapeutic agents cyclophosphamide or melphalan had strong negative effects on MSC expansion and CD44 expression. In addition, changes were seen in the ability of MSCs to support hematopoietic cell migration and repopulation. These observations therefore highlight potential disadvantages in the use of autologous MSCs in chemotherapeutically pre-treated patients for future therapeutic strategies. Furthermore, this study suggests that if the damage caused by chemotherapeutic agents to marrow MSCs is substantial, it would be logical to use cultured allogeneic MSCs therapeutically to assist or repair the marrow microenvironment after HDC.

Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy.

Hematopoietic recovery after high-dose chemotherapy (HDC) in the treatment of hematological diseases may be slow and/or incomplete. This is generally attributed to progressive hematopoietic stem cell failure, although defective hematopoiesis may be in part due to poor stromal function. Chemotherapy is known to damage mature bone marrow stromal cells in vitro, but the extent to which marrow mesenchymal stem cells (MSCs) are damaged by HDC in vivo is largely unknown. To address this question, the phenotype and functional properties of marrow MSCs derived from untreated and chemotherapeutically treated patients with hematological malignancy were compared. This study demonstrates a significant reduction in MSC expansion and MSC CD44 expression by MSCs derived from patients receiving HDC regimens, thus implicating potential disadvantages in the use of autologous MSCs in chemotherapeutically pretreated patients for future therapeutic strategies. The clinical importance of these HDC-induced defects we have observed could be determined through prospective randomized trials of the effects of MSC cotransplantation on hematopoietic recovery in the setting of HDC with and without hematopoietic stem cell rescue.

Outcomes in retinoblastoma, 1974-2005: the Children's Hospital, Westmead.

BACKGROUND: To report the 31-year experience of outcomes in retinoblastoma from a single centre. METHODS: A retrospective analysis of consecutive cases of retinoblastoma diagnosed and treated at the Westmead Children's Hospital, Sydney between 1974 and 2005 was performed. The subjects were analysed as two groups: those diagnosed between 1974 and 1989 (series alpha) and those diagnosed between 1990 and 2005 (series beta). RESULTS: There were a total of 142 patients included in the study, with a median follow up of 72 months. There were 84 patients with unilateral disease and 58 patients (116 eyes) with bilateral disease. The total enucleation rate remained high throughout both series for those with unilateral disease: 89% (series alpha) and 95% (series beta). There was a reduction in enucleations performed for those with bilateral disease from 68.4% (series alpha) to 43.6% (series beta) (P < 0.025). There were no bilateral enucleations performed after 1995. Actuarial Kaplan-Meier curves showed that 56% of all preserved eyes had not recurred at a median follow up of 95 months and 78.1% had avoided enucleation. Overall 43% of preserved eyes attained a visual acuity better than or equal to 6/12 and 55% achieved a visual acuity better than 6/60. There were four deaths due to retinoblastoma. Five patients were diagnosed with a second non-ocular malignancy. The most common treatment-related complications were cataracts, facial deformity, sepsis and febrile neutropaenia. CONCLUSIONS: The introduction of newer globe-preserving treatments for retinoblastoma was associated with equivalent visual outcomes, stable mortality rate and a greater number of short-term complications but avoided the late side-effects associated with external beam radiotherapy.

Retinoblastoma in New South Wales 1975 to 2001.

PURPOSE: To examine the epidemiology of retinoblastoma in New South Wales (NSW), from 1975 to 2001, comparing the incidence with other parts of the developed world. METHODS: Examination of medical files for patients presenting to NSW retinoblastoma treatment centers between 1975 and 2001. Comparisons to international data were made. RESULTS: One hundred twenty-eight patients [63 (49.2%) male and 65 (51.8%) female] presented. The mean annual incidence of retinoblastoma in NSW was 8 per million children aged 0 to 6 years, per year. CONCLUSIONS: The incidence of retinoblastoma in NSW is similar to other parts of the developed world.

The correlation between the percent of CD3- CD56+ cells and NK precursor function.

The number and function of human natural killer (NK) cells are generally assessed to monitor the baseline of immune function, the effect of treatment, the progress of malignancy or metastases and diseases. NK cells recognise and kill target cells in the absence of prior sensitisation and are able to defend the host from infection or prevent the progression of a disease. Human NK cells express CD16 and CD56 which are (massively) being used as a major hallmark for the NK cell. The purpose of this study was to identify the unique subsets of peripheral blood mononuclear cells (PBMC) (%CD3-CD56+ cells) by flow cytometry and to determine whether there is any correlation with functionally mature progeny of (NKp) precursor after five days of culture. The correlation was analysed using samples obtained from 120 Caucasian patients. 20-30ml of whole blood was collected in sterile tube containing preservative free sodium heparin and a similar sample was obtained after five days. Maturation of NKp required the continuous presence of recombinant interleukin 2 (rIL-2), or interleukin 15 (rIL-15) and functional maturity of NK cells was determined by their ability to lyse target cells from the K562 cell line. The NK precursor frequency was measured by limiting dilution analysis (LDA), which The NKpf assay was set up with a range of cell dilutions from 40,000 to 625 per 100ml/well in 96 well culture plates. At the end of the culture period the K562 cell line labelled with Europium (Eu-K562) was added and Eu release measured in culture supernatants using time-resolved fluorometry. The PBMC were set up in parallel cultures under various conditions . On day five cells were collected from culture plates and adjusted to 1x10 cells/ml and then mixed. The mixture was incubated and anti CD3 and anti CD56 were added. NK cells were enumerated in 120 patients by double staining with a combination of anti-CD3- and anti-CD56+. The results of these Immunophenotyping studies by flow cytometry showed no correlation between the NKpf (natural killer precursor frequency) and the percent of CD3-CD56+ cells expressed after five days confirming that CD56 was inadequate as a unique marker for functional NK cells.

Bone marrow-derived mesenchymal stem cells.

Human mesenchymal stem cells (MSCs) contribute to the regeneration of mesenchymal tissues, and are essential in providing support for the growth and differentiation of primitive hemopoietic cells within the bone marrow microenvironment. Techniques are now available to isolate human MSCs and manipulate their expansion in vitro under defined culture conditions without change of phenotype or loss of function. Mesenchymal stem cells have generated a great deal of interest in many clinical settings, including that of regenerative medicine, immune modulation and tissue engineering. Studies have already demonstrated the feasibility of transplanted MSCs providing crucial new cellular therapy. In this review, many aspects of the MSC will be discussed, with the main focus being on clinical studies that describe the potential of MSCs to treat patients with hematological malignancies who are undergoing chemotherapy and/or radiotherapy.

Management of Duane retraction syndrome.

BACKGROUND: Duane retraction syndrome is the most common cause of congenital aberrant ocular innervation. We report referral practices, clinical characteristics and complications, prevalence of congenital and familial anomalies, and management outcomes from a clinic-based series. METHODS: Retrospective clinic-based study of 65 patients with Duane retraction syndrome seen between January 1994 and March 2004. RESULTS: The majority of patients were girls with type I Duane retraction syndrome associated with esotropia in primary gaze. Twenty percent of cases were complicated by absent binocular stereoacuity and 16.9% had amblyopia. Family history of any ocular disorder was reported in 38.5% of cases, while an associated congenital abnormality was found in 46% of patients. There was a significant delay between the age when ocular abnormalities were first noticed and the age when patients presented at our tertiary referral center (P < .001). Twenty-two percent of patients underwent surgical correction at a mean age of 6 years. Most procedures were unilateral or bilateral medial or lateral rectus recessions. Postoperative ocular alignment < or = 15 prism diopters (PD) was achieved in 86% of cases, with 50% of cases having < or = 5 PD. CONCLUSIONS: Amblyopia and absent binocular stereo vision affected one in five patients with Duane retraction syndrome. There was significant delay between identification of an abnormality and presentation at the eye clinic.