First-in-human phase I study of SOR-C13, a TRPV6 calcium channel inhibitor, in patients with advanced solid tumors.

Introduction This was an open-label, dose escalation (3 + 3 design), Phase I study of SOR-C13 in patients with advanced tumors of epithelial origin. Primary objectives were to assess safety/tolerability and pharmacokinetics. Secondary goals were to assess pharmacodynamics and efficacy of SOR-C13. Methods SOR-C13 was administered IV QD on days 1-3 and 8-10 of a 21-day cycle. Doses were 2.75 and 5.5 mg/kg (20-min infusion) and 1.375, 2.75, 4.13 and 6.2 mg/kg (90-min infusion). Toxicity was assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Dose limiting toxicity (DLT) was assessed within the first treatment cycle. Tumors were evaluated, using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, after two cycles. Results Twenty-three patients were treated. No drug-related serious adverse events occurred. DLTs occurred in six patients: asymptomatic, drug-related, transient Grade 2 hypocalcemia (4 patients), and unrelated Grade 3 anemia and Grade 3 atrial fibrillation, 1 patient each. Calcium and vitamin D supplementation eliminated further Grade 2 hypocalcemia. One Grade 3 treatment emergent adverse event, urticaria, was definitely related to SOR-C13. Four possibly drug-related, Grade 3 events (alanine aminotransferase and aspartate aminotransferase elevation, headache, and hypokalemia) were observed. Of 22 evaluable patients, 54.5% showed stable disease ranging from 2.8 to 12.5 months. The best response was a 27% reduction in a pancreatic tumor with a 55% reduction in CA19-9 levels at 6.2 mg/kg. Conclusion SOR-C13 was safe and tolerated up to 6.2 mg/kg. The Maximal Tolerated Dose (MTD) was not established. Stable disease suggested antitumor activity.

Is cataract associated with cardiovascular morbidity?

AIMS: To evaluate the prevalence of cardiovascular disease (CVD) and its risk factors among patients undergoing cataract surgery. METHODS: A retrospective observational case-control study of all the members older than 50 years who underwent cataract surgery in the Central District of Clalit Health Services in Israel (years 2000-2007) (n=12,984) and 25, 968 age- and gender-matched controls. We calculated the prevalence of CVDs' and their risk factors, including carotid artery disease (CAD), peripheral vascular disease (PVD), systemic arterial hypertension (HTN), chronic renal failure (CRF), ischaemic heart disease (IHD), congestive heart failure, diabetes, smoking, alcohol abuse, and hyperlipidaemia. The main outcome measures were the odds ratio of having CVDs among cataract patients undergoing surgery compared with controls. RESULTS: No difference was found in demographics (age, gender, marriage status, socioeconomic class, and living place) between the study and control groups. All CVDs' risk factors were significantly more prevalent in cataract patients in univariate analysis. Multivariate logistic regression analysis revealed a significant association of the following with cataractogenesis: diabetes, CAD, HTN, PVD, smoking, IHD, CRF, hyperlipidaemia, and Ashkenazi origin. CONCLUSIONS: CVDs and their risk factors are more prevalent among cataract patients undergoing cataract surgery.

Lacrimal drainage obstruction and dacryocystorhinostomy in children.

PURPOSE: To determine the outcome of dacryocystorhinostomy (DCR) for nasolacrimal duct obstruction (NLDO) in children. METHODS: A review of medical records of 104 cases (82 patients) of paediatric DCR who underwent DCR at the Sydney Eye Hospital from 1995 to 2004. The main outcome measures included post-operative symptomatic relief of presenting symptoms, complications, subjective visibility of any scar, and general satisfaction. Statistical methods included chi(2) tests, and Student's t-tests for the comparison of variables among groups. RESULTS: Ninety-four external, 10 endoscopic primary procedures, and five revision procedures were included. Fifty-six of the cases were primary NLDO, and 48 were secondary NLDO. The mean follow-up was 1.44 years. Average age at surgery was 6.6+/-4.2 years (mean+/-SD). Ninety-one eyes needed DCR for the involvement of the lower lacrimal outflow system, and 13 eyes were NLDO associated with congenital punctual/canalicular dysgenesis.Most of the complications of external DCR were related to Jones tube placement. Five cases (4.8%) needed DCR revision. There was a significantly higher incidence of revision surgery in the non-stented group (P<0.01), and the Jones tube group (P<0.001) as compared with the silicone intubation stent group. CONCLUSIONS: External DCRs have acceptable long-term clinical and cosmetic results, and low post-operative complication rate. Cases with punctal stenosis or those requiring Jones tube insertion are associated with a higher complication rate. Silicone intubation is associated with a lower need for operative revision.

Idiopathic orbital inflammatory syndrome: clinical features and treatment outcomes.

AIM: To characterise the clinical and pathological features of 24 patients with biopsy proven Idiopathic Orbital Inflammatory Syndrome (IOIS). METHODS: Retrospective case series. RESULTS: The study included 14 men and 10 female patients, ranging in age from 14 to 75 years. The presenting symptoms and signs included pain (14/24), swelling/mass (19/24), diplopia (9/24), proptosis (15/24), extraocular muscle restriction (13/24), decreased vision (5/24) and ptosis (4/24). Histopathology was varied and included classical orbital pseudotumour (9/24), sclerosing orbital pseudotumour (13/24), vasculitic orbital pseudotumour (1/24) and granulomatous orbital pseudotumour (1/24). Treatments included oral steroids (19/24), intravenous steroids (1/24), methotrexate, azathioprine, mycophenalate and ciclosporin. Forty-two per cent of the patients had recurring episodes during the follow-up period, with 29% of patients requiring two or more treatment regimens to maintain remission. Two-thirds of patients (16/24) had complete resolution of their symptoms and signs. There was no correlation between the histopathological subtype, relapse rate or symptoms and resolution of signs. CONCLUSION: Idiopathic Orbital Inflammatory Syndrome has variable clinical and pathological features. Although, in some patients, symptoms and signs resolve spontaneously, most require treatment with oral steroids and additional immunosuppressant drugs or radiotherapy. The clinical and pathological features do not correlate with treatment outcomes.

Refractive surgery for refractive errors which cause strabismus. A report of 8 cases.

PURPOSE: While excimer laser refractive surgery is a well known procedure for correcting refractive errors, its use in adult patients with accommodative or partially accommodative esotropia who wish to remove their glasses, and those with high anisometropia and exotropia has not been extensively studied. We report our experience treating these two conditions with refractive surgery. METHODS: A retrospective review of the records of 8 adult patients with stable refractive error who underwent refractive surgery by the LASIK procedure. Three patients had accommodative esotropia, 3 had partially accommodative esotropia, and two patients had myopic anisometropia and exotropia. RESULTS: The LASIK refractive treatment corrected the strabismic deviation related to the hyperopia in the accommodative and partially accommodative esotropic patients. It also corrected the exotropia in the myopic anisometropic patients with exotropia. CONCLUSIONS: Refractive surgery is effective in treating accommodative and partially accommodative esotropia in adults and in cases of myopic anisometropia with exotropia.

Counting reticulocytes by flow cytometry: use of thiazole orange.

Thiazole orange is a new fluorescent dye which will bind to the residual RNA in the cytoplasm of reticulocytes and allow their enumeration by FACS analysis. We have evaluated the use of this dye in the routine haematology laboratory. There is an excellent correlation between manual and FACS reticulocyte counts (r = 0.98) but FACS counting showed significantly higher precision (CV = 3.1) than the manual method (CV = 11.9) for single observer, 20.8% for multiple observers). Clinical specimens showed stable reticulocyte counts for 6 h if stored at 4 degrees C allowing efficient batching of samples. There was a significant fall in reticulocyte counts stored for 24 h at both 4 degrees C and 21 degrees C. Evaluation of 78 male and 76 female blood donors by FACS analysis gave normal ranges (mean % +/- 2 SD) of 0.74 +/- 0.48 and 0.84 +/- 0.56 respectively (P less than 0.005). When corrected to absolute values there was no sex difference (36 +/- 24 x 10(9)/l). Thiazole orange is an effective stain for the automated counting of reticulocytes by FACS analysis.