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Purpose: To determine rates of intraoperative and postoperative systemic and ocular adverse events and establish the value of preoperative medical assessment in patients undergoing surgery for primary rhegmatogenous retinal detachment repair at a single academic center., Patients and Methods: Retrospective cohort study of 185 patients undergoing surgery for repair of primary rhegmatogenous retinal detachment (RRD) at a single academic center. Medical records were reviewed for medical comorbidities, completion of preoperative medical examination, anesthesia used during surgery, intraoperative adverse medical events, intraoperative ocular complications, and systemic and ocular postoperative complications. The main outcome of interest was the association of comorbidities and preoperative medical evaluation with intraoperative and postoperative complications., Results: Approximately 48% of the patients presented with no medical comorbidities of interest. Formal preoperative evaluation by an independent medical provider was completed in 36% of the patients. Overall, intraoperative and postoperative systemic complications (5.7% and 1%, respectively) and intraoperative and postoperative ocular complications (0.5% for both) were uncommon. Patients with a history of chronic heart failure (OR 24.5, P =0.02) or who received general anesthesia (OR 9.56, P <0.001) had increased risk of having experienced any intraoperative or postoperative complication. No relationship between preoperative medical evaluation and intraoperative and postoperative complications was observed., Conclusion: Patients undergoing surgery for RRD repair presented with fewer medical comorbidities than previously reported in patients undergoing all vitreoretinal surgeries. Intraoperative and postoperative complications were uncommon and were increased in patients with chronic heart failure or who received general anesthesia. Complications were not significantly associated with preoperative evaluation by an independent medical provider., Competing Interests: Dr Robison Vernon Paul Chan reports personal fees from Allergan, Alcon, Visunex Medical Systems, Beyeonics, and Genentech outside the submitted work. Dr Szilard Kiss reports personal fees and a stock grant from Adverum, and personal fees from Alcon, Optos, RegenXBio, BioMarin, Regeneron, Novartis, Genentech/Roche, and Fortress Bio during the conduct of the study. Dr Donald J. D’Amico reports grants from Research to Prevent Blindness, Inc. during the conduct of the study. The authors report no other conflicts of interest in this work., (© 2019 Alabi et al.)

Purpose : Retinopathy of prematurity (ROP) is widely regarded worldwide as a major cause of childhood blindness, however until recently the disease has not been recognized in most of the African continent. As a result of changing economic conditions, there is growing evidence that the population at risk for ROP in Africa is increasing. This report aims to summarize the published literature on ROP from Africa. Methods : We performed a systematic literature review of the English and French online literature databases by applying a general search strategy initially on May 1, 2017 with repeat inquiry on May 20, 2018. Search phrases included multiple variants of terms including "ROP", "retinopathy of prematurity", in conjunction with each of the individual 54 recognized sovereign African states. Findings : A total of 25 individual studies from six African nations were identified: South Africa (10), Egypt (7), Nigeria (4), with the nations of Sudan, Rwanda, and Kenya each having one respective study. Two countries (South Africa and Kenya) have developed national ROP policies for primary and secondary prevention. Summary : Review of the published literature suggests that ROP is emerging in Africa, however, there are published data from 6/54 (11%) African nations. Blindness from ROP is often preventable with appropriate primary and secondary prevention. This report provides compelling evidence that these efforts should be undertaken to implement and evaluate regionally appropriate ROP prevention programs in a growing number of African countries.

Purpose of Review: An update and overview of the literature on current telemedicine applications in retina., Recent Findings: The application of telemedicine to the field of Ophthalmology and Retina has been growing with advancing technologies in ophthalmic imaging. Retinal telemedicine has been most commonly applied to diabetic retinopathy and retinopathy of prematurity in adult and pediatric patients respectively. Telemedicine has the potential to alleviate the growing demand for clinical evaluation of retinal diseases. Subsequently, automated image analysis and deep learning systems may facilitate efficient processing of large, increasing numbers of images generated in telemedicine systems. Telemedicine may additionally improve access to education and standardized training through tele-education systems., Summary: Telemedicine has the potential to be utilized as a useful adjunct but not a complete replacement for physical clinical examinations. Retinal telemedicine programs should be carefully and appropriately integrated into current clinical systems., Competing Interests: Conflict of Interest Ru-ik Chee, Dana Darwish, Alvaro Fernandez-Vega, Samir Patel, Karyn Jonas, Susan Ostmo, Peter Campbell, and R.V. Paul Chan declare no conflict of interest.

Objectives: To evaluate the effects of goal-directed therapy on outcomes in high-risk patients undergoing cardiac surgery., Design: A prospective randomized controlled trial and an updated metaanalysis of randomized trials published from inception up to May 1, 2015., Setting: Surgical ICU within a tertiary referral university-affiliated teaching hospital., Patients: One hundred twenty-six high-risk patients undergoing coronary artery bypass surgery or valve repair., Interventions: Patients were randomized to a cardiac output-guided hemodynamic therapy algorithm (goal-directed therapy group, n = 62) or to usual care (n = 64). In the goal-directed therapy arm, a cardiac index of greater than 3 L/min/m was targeted with IV fluids, inotropes, and RBC transfusion starting from cardiopulmonary bypass and ending 8 hours after arrival to the ICU., Measurements and Main Results: The primary outcome was a composite endpoint of 30-day mortality and major postoperative complications. Patients from the goal-directed therapy group received a greater median (interquartile range) volume of IV fluids than the usual care group (1,000 [625-1,500] vs 500 [500-1,000] mL; p < 0.001], with no differences in the administration of either inotropes or RBC transfusions. The primary outcome was reduced in the goal-directed therapy group (27.4% vs 45.3%; p = 0.037). The goal-directed therapy group had a lower occurrence rate of infection (12.9% vs 29.7%; p = 0.002) and low cardiac output syndrome (6.5% vs 26.6%; p = 0.002). We also observed lower ICU cumulative dosage of dobutamine (12 vs 19 mg/kg; p = 0.003) and a shorter ICU (3 [3-4] vs 5 [4-7] d; p < 0.001) and hospital length of stay (9 [8-16] vs 12 [9-22] d; p = 0.049) in the goal-directed therapy compared with the usual care group. There were no differences in 30-day mortality rates (4.8% vs 9.4%, respectively; p = 0.492). The metaanalysis identified six trials and showed that, when compared with standard treatment, goal-directed therapy reduced the overall rate of complications (goal-directed therapy, 47/410 [11%] vs usual care, 92/415 [22%]; odds ratio, 0.40 [95% CI, 0.26-0.63]; p < 0.0001) and decreased the hospital length of stay (mean difference, -5.44 d; 95% CI, -9.28 to -1.60; p = 0.006) with no difference in postoperative mortality: 9 of 410 (2.2%) versus 15 of 415 (3.6%), odds ratio, 0.61 (95% CI, 0.26-1.47), and p = 0.27., Conclusions: Goal-directed therapy using fluids, inotropes, and blood transfusion reduced 30-day major complications in high-risk patients undergoing cardiac surgery.

Purpose: To describe ultra-widefield fluorescein angiography (UWFA) findings in eyes with white without pressure (WWOP) and in eyes without any obvious peripheral chorioretinal disease, and to determine if a difference exists between these two groups., Methods: A retrospective review of 379 eyes undergoing diagnostic UWFA using the Optos 200Tx imaging system. Eyes were excluded if the quality of the color photograph or UWFA prevented reliable evaluation. Eyes were also excluded if there was any evidence of peripheral retinal or choroidal disease, which was thought to have an effect on UWFA (eg, peripheral background diabetic or hypertensive retinopathy, vein occlusion, or any other peripheral vascular disorder). Eyes were determined to have WWOP, based on a dilated fundus examination and color fundus photography that contained areas of peripheral retinal whitening consistent with the diagnosis. UWFA was evaluated by trained masked graders, and determined to have or not have peripheral vascular leakage and/or staining., Results: Of the 379 eyes evaluated, 45 eyes were included in the study. Twelve eyes were determined to have peripheral WWOP; 33 eyes did not have WWOP on examination or color fundus photography. Three common UWFA peripheral patterns were visualized. Eyes with and without WWOP were grouped into one of three patterns. The majority of eyes without WWOP demonstrated UWFA pattern one (69.7%), while those in the WWOP group demonstrated pattern three (50%). The distribution of UWFA patterns is statistically different between those with and without WWOP (P = 0.002). In eyes without WWOP, in patients with no documented systemic microvascular disease (diabetes, hypertension), 71.4% of eyes had UWFA pattern one while 14.3% had both patterns two and three., Conclusion: This study is one of the first to specifically evaluate peripheral vascular leakage/staining in eyes with WWOP as well as in eyes without any obvious peripheral chorioretinal disease. We demonstrate that a significant portion of WWOP eyes exhibit peripheral findings on UWFA (pattern one) compared to eyes without WWOP. Importantly, even in eyes that are apparently unremarkable in the periphery on exam and color photography, UWFA can still show peripheral vascular abnormalities. These results warrant further investigation.

Purpose. To evaluate the clinical features, microbiological spectrum, and treatment outcomes of endogenous endophthalmitis. Methods. Retrospective review of consecutive cases with infective endogenous endophthalmitis presenting from 2000 to 2007. The main outcome measure was the visual outcome at the latest follow-up visit. Other outcome measures included microbiological investigations, anatomical and clinical outcomes. Results. 22 eyes of 21 patients were included, and the mean follow-up duration was 2.7 years. Eyes with fungal endogenous endophthalmitis were more likely to have visual acuity of finger counting or better at presentation compared with those with bacterial endogenous endophthalmitis (odds ratio = 15.0, P = 0.013). Gram-negative microorganisms accounted for 50% of infections, while fungal and gram-positive organisms accounted for 27.3% and 22.7%, respectively. Despite treatment, the visual outcome was poor in general as 10 (45.5%) eyes had no light perception at the latest follow-up visit and 6 (27.3%) eyes required enucleation or evisceration. Contrary to previous studies, fungal endogenous endophthalmitis did not appear to have better visual outcome compared with bacterial endogenous endophthalmitis. Conclusion. Gram-negative microorganisms were the main causative pathogens of endogenous endophthalmitis in Hong Kong. The visual prognosis of endogenous endophthalmitis is generally poor as almost 50% of eyes were blind despite treatment.

Pulmonary arteriovenous malformations (PAVMs) can cause stroke, brain abscess or life-threatening haemorrhage. Most PAVMs are associated with hereditary haemorrhagic telangiectasia (HHT). The aim of the present study was to describe the clinical presentation and treatment outcomes of those with idiopathic PAVMs, which has not previously been described in the literature. Patients with idiopathic PAVMs were identified at our HHT centre. Retrospective review of charts and imaging were performed. 20 patients were identified with idiopathic PAVMs. The most common symptoms reported were dyspnoea and migraines (50 and 30% of patients, respectively). Previous complications of PAVMs included haemoptysis (20%), stroke (20%) and brain abscess (5%). A total of 28 focal PAVMs were identified. Most patients (80%) had a solitary PAVM. 13 out of 28 PAVMs (46%) were located in the lower lobes. Most were simple and fistulous rather than complex and plexiform. Transcatheter embolotherapy was performed in 17 patients and was successful in improving oxygenation in all cases. The clinical manifestations and complications of idiopathic PAVMs are similar to those associated with HHT. Idiopathic PAVMs are anatomically similar to HHT-related PAVMs except for a greater number of solitary PAVMs and a lack of lower lobe predominance. Transcatheter embolotherapy is a safe and effective method for treating idiopathic PAVMs.

Purpose: To evaluate the outcome of verteporfin photodynamic therapy (PDT) with or without intravitreal triamcinolone acetonide (IVTA) for the treatment of symptomatic polypoidal choroidal vasculopathy (PCV)., Methods: Retrospective analysis of PCV patients who underwent PDT with or without IVTA with follow-up of 2 or more years. Changes in best-corrected visual acuity (BCVA), proportion of eyes with moderate visual loss (3 or more lines), and complications were compared between patients with or without IVTA., Results: Twenty-seven eyes of 27 patients were analyzed, with 12 eyes treated by PDT monotherapy and 15 eyes treated by combined PDT with IVTA. The baseline characteristics of both groups were similar. At 1 year, the mean logMAR BCVA for the PDT monotherapy group improved from 0.74 to 0.58 (P = 0.011), whereas the combined PDT and IVTA group improved from 0.84 to 0.74 (P = 0.17). At 2 years, the mean logMAR BCVA for the monotherapy and combined treatment groups were 0.62 and 0.84, respectively, and the changes compared with baseline were not statistically significant. No significant difference was found in the mean logMAR BCVA, the mean line of visual changes, and the mean number of PDT treatments between the 2 groups at 1 and 2 years. One (8.3%) and 4 (26.7%) eyes in the monotherapy and the combined groups lost 3 or more lines at 2 years, respectively. Patients who had combined PDT with IVTA were more likely to develop cataract requiring surgery and ocular hypertension (P = 0.043 and 0.046, respectively)., Conclusions: PDT reduced the risks of visual loss in patients with symptomatic PCV in the short term but the effect might not be sustained after 1 year. The adjunctive use of IVTA during PDT did not appear to result in additional benefit for treating PCV.

Purpose: To evaluate the effects of the duration of oral corticosteroid treatment on the recurrence of inflammation in Vogt-Koyanagi-Harada (VKH) disease., Methods: Retrospective analysis of 35 VKH patients who received oral corticosteroid during the first attack of VKH with a minimum follow-up of 6 months. Patients were divided into two groups on the basis of the oral corticosteroid treatment duration of less than 6 months or 6 months or more. Kaplan-Meier survival and Cox-regression analyses were carried out to compare the recurrence rates of inflammation in the two groups., Results: The mean age of onset was 42.5 years and the mean follow-up duration was 3.6 years. During the follow-up period, 10 (58.8%) of the 17 patients who received oral corticosteroid for less than 6 months compared with 2 (11.1%) of the 18 patients who had treatment for 6 months or more developed recurrence of inflammation (P=0.003). Cox-regression analysis showed that the duration of oral corticosteroid treatment for less than 6 months was the only significant risk factor for recurrence of VKH after adjustment for age, gender, and the initial dosage of oral corticosteroid treatment (adjusted odds ratio=8.8, P=0.008). Patients who received oral corticosteroid treatment for less than 6 months were also more likely to have one eye with visual acuity of 20/200 or worse (P=0.016)., Conclusions: Early withdrawal of oral corticosteroid is associated with increased risk of recurrence of VKH and worse visual prognosis. Oral corticosteroid should be tapered off slowly and maintained for at least 6 months for the treatment of acute VKH.

Background: The objective of this study was to investigate the relationship between different target levels of glucose and the clinical outcomes of patients undergoing cardiac surgery with cardiopulmonary bypass., Methods: We designed a prospective study in a university hospital where 109 consecutive patients were enrolled during a six-month period. All patients were scheduled for open-heart surgery requiring cardiopulmonary bypass. Patients were randomly allocated into two groups. One group consisted of 55 patients and had a target glucose level of 80-130 mg/dl, while the other contained 54 patients and had a target glucose level of 160-200 mg/dl. These parameters were controlled during surgery and for 36 hours after surgery in the intensive care unit. Primary outcomes were clinical outcomes, including time of mechanical ventilation, length of stay in the intensive care unit, infection, hypoglycemia, renal or neurological dysfunction, blood transfusion and length of stay in the hospital. The secondary outcome was a combined end-point (mortality at 30 days, infection or length of stay in the intensive care unit of more than 3 days). A p-value of <0.05 was considered significant., Results: The anthropometric and clinical characteristics of the patients from each group were similar, except for weight and body mass index. The mean glucose level during the protocol period was 126.69 mg/dl in the treated group and 168.21 mg/dl in the control group (p<0.0016). There were no differences between groups regarding clinical outcomes, including the duration of mechanical ventilation, length of stay in the intensive care unit, blood transfusion, postoperative infection, hypoglycemic event, neurological dysfunction or 30-day mortality (p>0.05)., Conclusions: In 109 patients undergoing cardiac surgery with cardiopulmonary bypass, both protocols of glycemic control in an intraoperative setting and in the intensive care unit were found to be safe, easily achieved and not to differentially affect clinical outcomes.

Background: Untreated pulmonary arteriovenous malformations (PAVMs) can present with life-threatening complications. Agitated saline solution transthoracic contrast echocardiography (TTCE) has been recommended as the screening test of choice for PAVMs in hereditary hemorrhagic telangiectasia (HHT). A TTCE grading system has been proposed but not validated. The aim of this study was to determine the positive predictive value (PPV) of TTCE grades for the presence of PAVMs on CT., Methods: A blinded retrospective review was conducted. All patients screened at the Toronto HHT Center (June 2002 to September 2004) with positive TTCE results were included. TTCE results were scored for delay (number of cardiac cycles) before appearance of microcavitations in the left atrium and graded for intensity of opacification. Grade 1 indicates minimal left ventricular opacification, grade 2 indicates moderate opacification, grade 3 indicates extensive opacification without outlining the endocardium, and grade 4 indicates extensive opacification with endocardial definition. Thoracic CT was performed in all patients, and results were scored as positive, negative, or indeterminate for PAVMs., Results: Of 155 patients screened for PAVMs, 104 had positive TTCE results. Complete data were available for 90 patients (87%). Mean age was 45 years; 62% were female. Seventeen percent of patients screened and 27% of patients with positive TTCE results had CT detectable PAVMs. There was a significant association between TTCE grade and presence of PAVMs on CT (p < 0.0001). The PPV of grades 1, 2, 3, and 4 were 0.02 (95% confidence interval, 0.00 to 0.06), 0.25 (95% confidence interval, 0.06 to 0.44), 0.56 (95% confidence interval, 0.23 to 0.88), and 1.0 (95% confidence interval, 1.0 to 1.0), respectively., Conclusions: Increased shunt grade predicts increased probability of PAVMs and may be used to guide decisions in the screening algorithm for PAVMs.

Purpose: To describe the mechanisms and risk factors associated with reperfusion of successfully treated pulmonary arteriovenous malformations (PAVMs) after embolotherapy., Materials and Methods: Among 112 consecutive patients with PAVMs treated by embolotherapy, 19 patients were identified who had 33 angiographically confirmed reperfused PAVMs. A retrospective analysis of computed tomography (CT) and angiography was performed in patients with documented reperfused PAVMs in which reperfused PAVMs were compared with nonreperfused PAVMs. CT images were examined for persistence of the aneurysm and/or draining vein after initial embolotherapy and correlated with angiography to determine the mechanism of reperfusion. PAVM and embolic agent characteristics (eg, feeding artery size and number; PAVM location; coil size, number, and location) were evaluated for association with reperfusion. The outcomes of repeat embolotherapy for reperfused PAVMs were evaluated., Results: The PAVM aneurysm and/or draining vein persisted on CT after initial embolotherapy in all reperfused PAVMs and resolved in all nonreperfused PAVMs (in patients with nondiffuse PAVMs). Recanalization was the mechanism of reperfusion in 88%. Reperfusion was associated with the use of a single coil (P < .0001), oversized coils (P < .0001), coil placement more than 1 cm from the aneurysm (P < .0001), and increased feeding artery size (P < .001). Repeat embolotherapy for reperfused PAVMs was technically successful in 94% of cases. In the remaining 6% of cases, insufficient feeding artery length prevented safe repeat treatment. After a mean follow-up of 41 months, 42% of reperfused PAVMs in our series have been successfully treated again and occluded., Conclusions: Recanalization is the most common mechanism of PAVM reperfusion. Increased feeding artery diameter, low number of coils, use of oversized coils, and proximal coil placement within the feeding artery are associated with reperfusion. Distal coil placement facilitates repeat embolization if reperfusion occurs.

We describe a case of reperfusion of an aneurysm of the pancreaticoduodenal artery following transcatheter coil embolotherapy. The lesion was successfully treated by direct puncture of the aneurysm under computed tomographic guidance, followed by injection of thrombin. This technique is useful when an endovascular approach is not feasible.

Purpose: To compare the results of embolotherapy of pulmonary arteriovenous malformations (PAVMs) with use of platinum versus stainless-steel coils., Materials and Methods: From a database of 78 consecutive patients with PAVMs treated by embolotherapy between May 1992 and September 2001, 54 patients with 306 PAVMs were selected for retrospective evaluation. Exclusion criteria were PAVMs with less than 12 months of follow-up computed tomography (CT) of the thorax (n = 15), embolotherapy with a mixture of embolic materials (n = 8), and repeat embolotherapy for previous treatment failures (n = 1). Successful treatment was defined as complete resolution of the aneurysm sac and draining vein on follow-up CT (all patients) and/or absence of contrast material flow through the PAVM on pulmonary angiography (n = 27)., Results: Of 267 PAVMs embolized with stainless-steel coils, 249 (93.3%) were successfully occluded (mean follow-up, 3.1 years). Of 39 PAVMs embolized with platinum coils, 35 (89.7%) were successfully occluded (mean follow-up, 2.1 years). There was no significant difference in success between the two groups (P =.5). The mean feeding artery size was significantly larger (P <.0001) in the platinum group (4.3 mm) than in the stainless-steel group (3.5 mm). Potentially serious complications included coil reflux (n = 3), PAVM perforation (n = 2), self-limited neurologic deficit (n = 2), and systemic embolization of a coil (n = 1) in the stainless-steel group, and PAVM perforation (n = 2) in the platinum group. There were no long-term sequelae., Conclusions: Coil embolotherapy is highly efficacious, with no statistically significant difference between platinum and stainless-steel coils. The slightly higher proportion of sustained occlusion with stainless-steel coils may be partly explained by the larger mean feeding artery size in the platinum group. The study is limited by the small sample size of the platinum group.

Objective: To assess the safety and efficacy of radiofrequency ablation (RFA) in the treatment of malignant neoplasms of the liver., Methods: Sixty-seven patients received RFA for primary or secondary hepatic malignancies. Patients were followed prospectively with computed tomography (CT) scanning to assess for therapeutic response, disease progression and complications., Results: Eighty-eight lesions were treated, including 57 hepatocellular carcinomas, 28 metastases, 2 cholangiocarcinomas and 1 hepatic plasmacytoma. Mean tumour size was 2.7 cm (range 0.5-6.9 cm). A total of 101 ablations were performed (66 percutaneously, 35 intraoperatively). Over a mean follow-up period of 142 days, results were available for 85 lesions. Local tumour control was achieved for 61 (72%) lesions, but new distant lesions developed in 6 of these cases. Residual disease was present in 20 (23%) lesions, and 4 (5%) lesions developed local recurrence. There were 10 complications, including 1 death in a patient who developed a liver abscess and subsequently died from hepatic failure., Conclusions: RFA is safe and effective in the treatment of hepatic malignancies. Local tumour control can be achieved in most cases; however, careful surveillance is important for detecting recurrent disease, as well as new lesions distant from the treated site.

Background and Objectives: Since the first reported anesthetic death, many attempts have been made to study the incidence of risk factors, complications and mortality associated to anesthesia and surgery. The estimated perioperative mortality risk varies from 0.05 to 10 cases per 10,000 anesthesias. This study aimed at reporting the incidence of anesthetic-surgical death in the first 24 hours, at our hospital., Methods: Charts had been reviewed from 82,641 surgeries performed in 1998 and 1999. Deaths were analyzed according to Edwards classification, and by age, gender, physical status, (ASA), type of surgery and anesthesia., Results: Cause of the deaths according to Edwards classification has shown that 91.04% were class V, 3.77% class VI, 2.13% class VII, 2.84% class IV and 0.23% were class I. Age above 65 years accounted for 1.48% of deaths; adults incidence was 0.48%; the incidence in children aged 1 to 12 years was 0.11%; in children aged 31 days to 1 year it was 1.29% and in neonates up to 30 days of life the incidence was 2.88%. Death ratio as compared to total deaths was 59.2% in adults, 30.2% in patients above 65 years of age, 2.8% at the age 1 to 12, 4% in patients with 31 days of life to 1 year and 3.8% in newborn babies. Males represented 66.3% of deaths and females 33.7%. The distribution by ASA physical status was: ASA I - 11.1%, ASA II - 5.2%, ASA III - 30.9%, ASA IV - 34.4% and ASA V - 18.4%. Emergency surgeries accounted for 67.2% of deaths and elective surgeries for 32.8%. General incidence of the deaths was 0.51% being the highest in cardiac (1.88%) and vascular (1.87%) surgeries., Conclusions: Anesthetic-surgical deaths in the years 1998 and 1999 were considered inevitable according to Edwards classification. The highest incidence of deaths was in neonates. Most deaths occurred in males, ASA III or above patients, and emergency vascular or cardiac surgeries.

Sulfasalazine appears to exert its beneficial effect in colitis by releasing 5-aminosalicylic acid in the colon, but its use can be limited by side effects. Ipsalazide and balsalazide are novel sulfasalazine analogs designed to release 5-aminosalicylic acid and a nontoxic carrier molecule in the gastrointestinal tract. They have a low oral toxicity following single or repeat administration to mouse, rat, and ferret, and balsalazide is not mutagenic in the Ames test. Ipsalazide and balsalazide are split in rat and man, and the urinary and fecal excretion pattern of the 5-aminosalicylic acid released is similar to that of sulfasalazine; the carrier molecules are absorbed to a lesser extent than the sulfapyridine derived from sulfasalazine. These two analogs deserve therapeutic trial.

The synthesis of monohydroxy- and dihydroxy-bifluranol, and of glucuronide and sulphate conjugates of bifluranol are described. Bifluranol administered orally to rats, ferrets and dogs at a dosage of 50 to 200 microgram kg-1 is mostly excreted in the faeces as unchanged bifluranol and bifluranol monosulphate, disulphate and monoglucuronide. The bifluranol is well absorbed and is mostly excreted in the bile, as six different conjugates, including a glucuronide sulphate found in all 3 species, and a glucuronide phosphate found only in ferret and dog bile. Hydroxylation of the aromatic rings occurs in the rat, to an extent of about 8% of the dose, but was not detected in ferret or dog.

The synthesis of bifluranol, a new fluorinated bibenzyl anti-androgen, and of 3H-labelled bifluranol is described. The absorption, distribution and excretion of bifluranol has been studied in mouse, rat, ferret and dog; it is readily absorbed following oral administration, but blood concentrations of the drug are low due to hepatic uptake and biliary excretion. Enterohepatic re-circulation occurs, but the drug is excreted primarily in the faeces and only small amounts appear in urine. This pattern of disposition and excretion is similar to that reported elsewhere for the bibenzyl, hexoestrol, and for the stilbene, diethylstilboestrol.