Astigmatism and visual recovery after phacoemulsification and conventional extracapsular cataract extraction

In this study we wanted to investigate the post-operative astigmatism and visual acuity after phacoemulsification and conventional extracapsular cataract surgery. Patients operated between April and June 1993 (n=150) were retrospectively analyzed. The patients were examined prior to surgery and at day 1, at day 10, and in week 6 post-operatively. The difference between the post-operative log mean visual acuity in the Phaco group and in the CECCE group was significant after 1 and 10 days, however it was not significant (p=0.191) after 6 weeks. The mean astigmatism was significantly less in the Phaco group than in the CECCE group during the whole post-operative check-up period. This study suggests that Phaco results in a lower post-operative astigmatism and an earlier visual rehabilitation compared to the CECCE technique.Abbreviations Phaco Phacoemulsification - CECCE Conventional extracapsular cataract extraction     

When poor solubility becomes an issue: From early stage to proof of concept

Drug absorption, sufficient and reproducible bioavailability and/or pharmacokinetic profile in humans are recognized today as one of the major challenges in oral delivery of new drug substances. The issue arose especially when drug discovery and medicinal chemistry moved from wet chemistry to combinatorial chemistry and high throughput screening in the mid-1990s. Taking into account the drug product development times of 8–12 years, the apparent R&D productivity gap as determined by the number of products in late stage clinical development today, is the result of the drug discovery and formulation development in the late 1990s, which were the early and enthusiastic times of the combinatorial chemistry and high throughput screening. In parallel to implementation of these new technologies, tremendous knowledge has been accumulated on biological factors like transporters, metabolizing enzymes and efflux systems as well as on the physicochemical characteristics of the drug substances like crystal structures and salt formation impacting oral bioavailability. Research tools and technologies have been, are and will be developed to assess the impact of these factors on drug absorption for the new chemical entities.

The conference focused specifically on the impact of compounds with poor solubility on analytical evaluation, prediction of oral absorption, substance selection, material and formulation strategies and development. The existing tools and technologies, their potential utilization throughout the drug development process and the directions for further research to overcome existing gaps and influence these drug characteristics were discussed in detail.     

Platelet aggregation,disc haemorrhage and progressive loss of visual fields in glaucoma

Platelet aggregationin vitro, deterioration of visual field defects (VFD) and the prevalence of disc haemorrhages (DH) were assessed in 49 patients with primary open angle glaucoma (POAG) and compared with the findings for 67 individuals with suspected glaucoma (GS) in a seven-year follow-up study (range 5.8 to 8.2 years). The percentage patients with spontaneous platelet aggregation (SPA) was higher for POAG patients with visual field deterioration (60%) than both POAG patients without progressive loss of visual fields (12.5%; P<0.005) and those with suspected glaucoma (22.4%; P<0.005). The occurrence of DH was higher among POAG patients with progressive loss of visual field (28%) compared to the GS group (8.4%; P<0.025) and the group of patients consisting of POAG patients without deterioration of VFD and GS (9.9%; P<0.05). DH also occurred more often in patients with low tension glaucoma (41.6%) than in the remaining POAG patients (13.5%; P<0.05). No relation between the patients with SPA and the patients with DH was observed.Abbreviations NPB normal platelet behavior - SPA spontaneous platelet aggregation - DH disc haemorrhage     

Extent and Localization of Changes in Upper Airway Caliber with Varying Concentrations of Sevoflurane in Children

Background: Previous studies in humans suggest that inhibition of upper airway muscle activity is independent of the dose of inhalational anesthesia. Whether a dose-independent relation applies to changes in airway caliber is unknown. The authors sought to evaluate the configurational changes that lead to upper airway narrowing during inhalational anesthesia with sevoflurane and to determine whether these changes are dose dependent within a clinically relevant dose range.

Methods: Fifteen children undergoing elective magnetic resonance imaging of the brain were studied. Magnetic resonance images of the upper airway were acquired at sevoflurane concentrations of 0.5, 1.0, and 1.5 minimum alveolar concentration (MAC), administered in random sequence. At least 15 min was allowed for equilibration of inspired and alveolar partial pressures of sevoflurane. Images were acquired in early expiration at the level of the soft palate, base of the tongue, and tip of the epiglottis. Airway cross-sectional area (CSA), anteroposterior, and transverse dimension were determined using image-analysis software.

Results: At each anatomical level, pharyngeal CSA decreased progressively with increasing depth of sevoflurane anesthesia (P < 0.001). Increasing the sevoflurane concentration from 0.5 to 1.0 MAC reduced airway CSA by 13-18%, and a further increase to 1.5 MAC resulted in an overall 28-34% reduction in CSA. The reduction in CSA was predominantly due to a decrease in anteroposterior dimension.     

CARD15 in inflammatory bowel disease and Crohn''s disease phenotypes: An association study and pooled analysis

BACKGROUND: Three major polymorphisms of the Caspase-Activation Recruitment Domain containing protein 15 gene have been described to be associated with Crohn's disease. Genotype-phenotype studies reported in literature provide conflicting data on disease localisation and behaviour. We investigated the relation of Caspase-Activation Recruitment Domain containing protein 15 with inflammatory bowel disease and Crohn's disease phenotypic characteristics in a large Dutch cohort and performed a pooled analysis on inflammatory bowel disease patients and Crohn's disease phenotypic characteristics reported in association studies. METHODS: We genotyped 781 cases and 315 controls for the R702W, G908R and 1007fsinsC variants and for six microsatellite markers in and close to Caspase-Activation Recruitment Domain containing protein 15. In the pooled analysis data of 7201 inflammatory bowel disease patients and 3720 controls from 20 studies were included. RESULTS: Association was found for Crohn's disease with R702W and 1007fsinsC, including several disease characteristics, and not for ulcerative colitis. In the pooled analysis all three common Caspase-Activation Recruitment Domain containing protein 15 variants showed strong association with Crohn's disease (p<0.00001; odds ratio varying from 3.0 for single heterozygotes to 14.7 for compound heterozygotes) and not with ulcerative colitis. Phenotype analysis showed association with small bowel involvement, stricturing and penetrating disease. CONCLUSION: Caspase-Activation Recruitment Domain containing protein 15 is associated with Crohn's disease and not with ulcerative colitis. All three common Crohn's disease-associated variants are associated with small bowel involvement, the G908R and 1007fsinsC alleles also being associated with a complicated disease course.     

The immunomodulatory effects of 3-monochloro-1,2-propanediol on murine splenocyte and peritoneal macrophage function in vitro.

3-Monochloro-1,2-propanediol (MCPD) is a well-known by-product of acid-hydrolyzed soy sauce during its manufacturing process. MCPD has been reported genotoxic in vitro, and reproductive toxicity and carcinogenicity in rats. To evaluate the immunomodulatory effect of MCPD on murine splenocyte and macrophage in vitro, we investigated splenocyte blastogenesis by concanavalin A (Con A), anti-CD3, and lipopolyssacharide (LPS), the production of cytokines from splenocyte, and the activity of mouse peritoneal macrophages. There was a significant decrease in lymphocyte blastogenesis to Con A or anti-CD3 at subtoxic dose of MCPD. A significant decrease in splenocyte blastogenesis to LPS was also observed. The production level of interferon (IFN)-gamma on splenocyte culture with Con A was significantly reduced at the higher concentration than 1.0mM of MCPD. The levels of interleukin (IL)-4 and IL-10 were also decreased at high concentrations of MCPD. There was a significant decrease in production of nitric oxide (NO) by peritoneal macrophages treated with MCPD. MCPD also inhibits tumor necrosis factor (TNF)-alpha production of stimulated macrophages. These results indicate that MCPD might be able to reduce the functionality of lymphocytes and peritoneal macrophages in vitro.     

Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide.

Scintigraphy with 123I-Tyr-3-octreotide has several major drawbacks as regards its metabolic behavior, its cumbersome preparation and the short physical half-life of the radionuclide. The use of another radiolabeled analog of somatostatin, 111In-DTPA-D-Phe-1-octreotide, has consequently been proposed. DTPA-D-Phe-1-octreotide can be radiolabeled with 111In in an easy single-step procedure. DTPA-D-Phe-1-octreotide is cleared predominantly via the kidneys. Fecal excretion of radioactivity amounts to only a few percent of the administered radioactivity. For the radiation dose to normal tissues, the most important organs are the kidneys, the spleen, the urinary bladder, the liver and the remainder of the body. The calculated effective dose equivalent is 0.08 mSv/MBq. Optimal 111In-DTPA-D-Phe-1-octreotide scintigraphic imaging of various somatostatin receptor-positive tumors was obtained 24 hr after injection. In the six patients studied, tumor localization with 123I-Tyr-3-octreotide and with 111In-DTPA-D-Phe-1-octreotide were found to be similar. However, the normal pituitary is more frequently visualized with the latter radiopharmaceutical. In conclusion, 111In-DTPA-D-Phe-1-octreotide appears to be a sensitive somatostatin receptor-positive tissue-seeking radiopharmaceutical with some remarkable advantages: easy preparation, general availability, appropriate half-life and absence of major interference in the upper abdominal region, because of its renal clearance. Therefore, 111In-DTPA-D-Phe-1-octreotide may be suitable for use in SPECT of the abdomen, which is important in the localization of small endocrine gastroenteropancreatic tumors.     

Anterior translocaton of pulmonary artery without aortic transection in repair of tetralogy of Fallot with absent pulmonary valve.

We developed a technique of translocation of the pulmonary artery anterior to the ascending aorta without transection of the aorta in the repair of tetralogy of Fallot with absent pulmonary valve. Our technique includes detachment of the main pulmonary artery (MPA) from the pulmonary annulus, vertical division of the MPA, anterior translocation of the pulmonary artery with patch augmentation between the vertically divided MPA.     

Visualization of maturation of the corpus callosum during childhood and adolescence using T2 relaxometry

Previous studies have shown that maturation of the white matter in terms of its relative signal intensity changes on MRI is almost complete at 2-3 years of age. We hypothesized that quantitative analysis may show maturation of the white matter during childhood and adolescence. In the present study we performed multi-echo T2 relaxometry in 33 healthy subjects (girls, 15; boys, 18) aged 3-15 years. T2 relaxation times of the genu and splenium were measured. In healthy subjects, the T2 relaxation times were significantly correlated with age in both girls (r=0.611, p=.016) and boys (r=0.721, p=.001) in the splenium, but not in the genu (p>.05). To further confirm genu-to-splenium signal intensity ratio changes, a total of 389 brain MRIs were retrospectively selected from the patients who had normal results (189 girls/women, 200 boys/men; age range, 3-20 years). The genu-to-splenium signal intensity ratio was obtained from the T2-weighted images. In patients with normal MRI, the genu-to-splenium signal intensity ratio was significantly decreased with age (p<.001) by 16 years. The T2 relaxation times gradually increase in the splenium during childhood and adolescence, suggestive of maturation.