ARE THE FACTORS AFFECTING ADVERSE PREGNANCY OUTCOMES DIFFERENT IN OBESE GESTATIONAL DIABETES PREGNANT WOMEN RECEIVING DIET OR INSULIN TREATMENT?

CONTEXT: We aimed to examine the factors affecting adverse gestational outcome in gestational diabetes (GDM) patients, who were grouped as obese and normal- weight, having only-diet, or insulin treatments. SUBJECTS AND METHODS: The study included 373 patients, treated with diet or insulin. These patients were sub-grouped as obese and non-obese, and examined retrospectively. The variables affecting adverse gestational outcome in obese GDM patients having dietary and/ or insulin treatments were detected with multiple regression analysis. RESULTS: The weight gained during pregnancy in the GDM group having insulin treatment was more than the one in only-diet treated GDM group (p=0.004). Pre-pregnancy body mass index, the weight gained during pregnancy, hemoglobin A1C levels in the second and third trimesters, caesarian rates were higher in the insulin-treated obese patients than in the other groups (p<0.001). The odds ratio for fasting blood glucose level in insulin-treated obese GDM group was 1.081 (95% CI =1.004 - 1.163) (p=0.039); and it was 0.982 (95% CI =0.924 - 1.002) (p=0.048) for the weight gained during pregnancy, in only-diet treated obese GDM patients. CONCLUSION: The control of weight gained during pregnancy, and of fasting blood glucose levels in obese patients having GDM, is important to decrease adverse gestational outcome.

The Value of Total antioxidant Status and Serum Tumor Necrosis Factor-α Levels at 24-28 Weeks of Gestation in the Prediction of Optimal Treatment Protocol in Gestational Diabetes Mellitus.

AIM: The aim of this study was to investigate the serum oxidative stress markers, antioxidant enzyme and tumor necrosis factor-α (TNF-α) levels at 24-28 weeks of gestation and to evaluate the predictive value of them on the subsequent treatment protocol in gestational diabetes mellitus (GDM). METHODS: A total of 58 GDM patients (30 treated with only conventional healthy dietary recommendation (CHDR), 28 treated with insulin) and 30 healthy pregnant women at 24-28 weeks of gestation, were enrolled in this prospective case-control study. The oxidative status, antioxidant enzyme and TNF-α levels were evaluated to determine if there is an association with the need of insulin therapy for glycemic control by using multivariable logistic regression analysis. RESULTS: TNF-α (OR=11.976, 95%CI: 2.441-58.754, P=0.002) and total antioxidant status (TAS) (OR=12.769, 95%CI: 2.464-66.182, P=0.002) were found to be predictive for GDM at 24-28 weeks of gestation. Besides, further evaluation considering the treatment modality showed that increased TNF-α (OR=18.615, 95%CI: 2.338-148.240, P=0.006) and lower TAS levels (OR=99.471, 95%CI: 2.865-3 453.061, P=0.011) were independent predictors of the need for insulin treatment in GDM patients. CONCLUSIONS: Increased TNF-α levels and low TAS are significantly associated with the increased risk of insulin requirement for achieving good glycemic control in GDM.

The role of ADAMTS4 and ADAMTS9 in cardiovascular disease in premature ovarian insufficiency and idiopathic hypogonadotropic hypogonadism.

PURPOSE: We aimed to determine the relation of a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4), and a disintegrin and metalloproteinase with thrombospondin motifs-9 (ADAMTS9) with cardiovascular disease (CVD) risk, in ovarian dysfunction patients with premature ovarian insufficiency (POI), and idiopathic hypogonadotropic hypogonadism (IHH). METHODS: 43 IHH and 44 POI patients were enrolled to this case-control study. Serum hormonal parameters, lipid profiles, ADAMTS4 and ADAMTS9 levels were measured. Lipid accumulation product (LAP) index, visceral adiposity index (VAI), and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. The patients with at least two out of the four following criteria were accepted to have increased CVD risk; waist-to-hip ratio (WHR) ≥ 0.8, waist circumference (WC) ≥ 79 cm, triglycerides (TG) ≥ 150 mg/dL, high-density lipoprotein cholesterol (HDL-C) < 50 mg/dL. Serum ADAMTS4 and ADAMTS9 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: ADAMTS4 and ADAMTS9 levels were significantly higher in the IHH group than the POI group (p = 0.002, and p = 0.013, respectively). IHH group had significantly higher levels of insulin, HOMA-IR index, and LAP index (p = 0.006, p = 0.005, and p = 0.013, respectively). The mean age of patients in the IHH group (23.60 ± 5.64 years) was significantly lower than the POI group (31.05 ± 6.03 years), (p < 0.001). Odds ratios (OR) were 1.236 (95% CI 1.055-1.447) and 1.002 (95% CI 1.000-1.004) for LAP index and ADAMTS4, respectively, in the IHH group. These two parameters found to have high predictivity for CVD risk in the IHH group (p = 0.009 and p = 0.028, respectively). CONCLUSION: The lower levels of ADAMTS4 in the POI group, when compared with the IHH patients pointed out that even limited hormone secretion and ovulation in the POI group, may have protective effect on cardiovascular system. The higher levels of ADAMTS4 and LAP index in the IHH group demonstrated the increased risk of these patients for CVD.

3Ds: decorin, discordance, and diamniotic dichorionic twins.

aullimary Investigation: The cause of discordance in dichorionic diamniotic (DD) twins is still unknown. The authors aimed to compare decorin (DCN) and oxidative/antioxidative state levels between the placentas of discordant and concordant twins. MATERIALS AND METHODS: Prospective study of 43 spontaneous DD twin pregnancies included and placentas samples taken from each twin and prepared for homogenization. Total oxidant/antioxidant status levels in placental tissue were determined by automated colorimetric method. Decorin levels were detected by using ELISA method; 23 of these were discordant and 20 of them were concordant. RESULTS: DCN levels in the placentas of the low birth-weight twins were significantly lower than the levels of the placentas of appropriate gestational age twins (p = 0.006). There were no statistically significant differences in total antioxidant status (TAS), total oxidant status (TOS), or arylesterase (ARES) levels in discordant (p = 0.631, p = 0.370, and p = 0.079, respectively) and in the placental DCN, TAS, TOS, or ARES levels of the concordant twins (p = 0.407, p = 0.035, p = 0.194, and p = 0.979, respectively). When the authors compared the twins of similar birth weight, the DCN, TAS, and TOS levels were significantly lower in the discordant twins (p < 0.001, p < 0.001, and p = 0.002, respectively). CONCLUSIONS: Decreased levels of DCN in discordant twin fetuses compared to the same birth weight-concordant twins shows that it contributes to disease pathogenesis.

3D bioprinting of biomimetic aortic vascular constructs with self-supporting cells.

Cardiovascular diseases are the leading cause of deaths throughout the world. Vascular diseases are mostly treated with autografts and blood vessel transplantations. However, traditional grafting methods have several problems including lack of suitable harvest sites, additional surgical costs for harvesting procedure, pain, infection, lack of donors, and even no substitutes at all. Recently, tissue engineering and regenerative medicine approaches are used to regenerate damaged or diseased tissues. Most of the tissue engineering investigations have been based on the cell seeding into scaffolds by providing a suitable environment for cell attachment, proliferation, and differentiation. Because of the challenges such as difficulties in seeding cells spatially, rejection, and inflammation of biomaterials used, the recent tissue engineering studies focus on scaffold-free techniques. In this paper, the development of novel computer aided algorithms and methods are developed for 3D bioprinting of scaffold-free biomimetic macrovascular structures. Computer model mimicking a real human aorta is generated using imaging techniques and the proposed computational algorithms. An optimized three-dimensional bioprinting path planning are developed with the proposed self-supported model. Mouse embryonic fibroblast (MEF) cell aggregates and support structures (hydrogels) are 3D bioprinted layer-by-layer according to the proposed self-supported method to form an aortic tissue construct.

Tilt and decentration of bag-fixated intraocular lenses: a comparative study between capsulorhexis and envelope techniques.

Malposition of an intraocular lens (IOL) may cause symptoms such as glare, halos, and other visual aberrations. The purpose of this study is to determine the effect of two different anterior capsulotomy techniques on IOL tilt and decentration. Bag-fixated IOL implantation after uncomplicated extracapsular cataract extraction was performed using both envelope (65 eyes) and continuous circular capsulorhexis (CCC) technique (42 eyes). Eyes were followed-up at least 6 months postoperatively. While the mean IOL decentration after envelope technique was found to be 0.65 mm, this was 0.15 mm after CCC technique. On the other hand, the mean actual tilting angle of IOL after envelope technique was 5.66 degrees, whereas this was 1.13 degrees after CCC technique. The aforementioned differences were statistically significant (p < 0.01, and p < 0.01). Furthermore, in 17 eyes (26.1%) where envelope technique and in 29 (69.0%) eyes where CCC technique was used demonstrated no IOL tilt and decentration. This study shows that the CCC technique may result in less optical problems due to IOL malposition compared to the envelope technique.

Indocyanine green-enhanced diode laser treatment of melanoma in a rabbit model.

Indocyanine green (ICG)-enhanced laser therapy was evaluated for the treatment of experimental intraocular melanoma. Immediately after an intravenous injection of ICG, a 790-nm chromophore, 810-nm semiconductor diode laser was used to irradiate Greene hamster melanomas that had been implanted in the iris of rabbits. ICG-enhanced laser treatment of melanoma (14 eyes) was compared with treatment by laser alone (4 eyes), ICG alone (1 eye), and no treatment (2 eyes). Tumors treated with ICG-enhanced laser showed no growth after treatment, as judged by clinical examination and photography. Histologically, 4 of the 14 tumors treated with ICG-enhanced laser showed total necrosis, whereas the remaining 10 tumors treated similarly demonstrated only rare viable cells around blood vessels or at the tumor periphery. Laser treatment without ICG enhancement resulted in only superficial tumor necrosis, and all four of these tumors continued to grow after treatment. With further evaluation, indocyanine green in combination with a commercially available diode laser may be useful in the treatment of ocular melanoma.

Pars plana vitrectomy for intraocular inflammation-related cystoid macular edema unresponsive to corticosteroids. A preliminary study.

PURPOSE: To determine the role of pars plana vitrectomy in patients with intraocular inflammation-related cystoid macular edema that is unresponsive to corticosteroids. METHODS: Eleven eyes of nine patients underwent a standard three-port pars plana vitrectomy. The primary indication was intraocular inflammation-related cystoid macular edema that was unresponsive to oral, sub-Tenon's, and topical corticosteroids. Preoperative follow-up ranged from 20 months to 144 months (average, 70 months). Postoperative follow-up ranged from 3 months to 108 months (average, 21 months). RESULTS: Seven eyes (64%) improved 4 or more lines of Snellen visual acuity within 4 weeks. Two eyes (18%) remained unchanged and 2 eyes (18%) worsened. Cystoid macular edema improved by clinical examination and fluorescein angiography in 9 eyes (82%) and by clinical examination alone in 2 eyes (18%). No intraoperative complications were noted. Postoperative complications consisted of cataract formation in 1 eye (9%), glaucoma in 2 eyes (18%), and epiretinal membrane formation in 1 eye (9%). CONCLUSION: Pars plana vitrectomy may have a role in the treatment of intraocular inflammation-related cystoid macular edema that fails to respond to corticosteroids. The subgroup of patients who benefit most remains to be identified.

Photodynamic therapy of experimental subchoroidal melanoma using chloroaluminum sulfonated phthalocyanine.

Although photodynamic therapy has shown great promise for the treatment of a variety of malignant neoplasms, the role of this new therapeutic modality in the clinical management of intraocular tumors remains incompletely understood. This study examines the effects of photodynamic therapy using chloroaluminum sulfonated phthalocyanine on Greene hamster melanoma transplanted into the subchoroidal space in rabbits. Twenty-four hours after intravenous administration of chloroaluminum sulfonated phthalocyanine (5 mg/kg), tumors were irradiated with 675 nm of light at total light doses of 7 to 60 J/cm2. The results show that tumor growth was arrested at total light doses of 22 to 60 J/cm2. At total light doses of 15 to 21 J/cm2, tumor growth was initially arrested. However, regrowth of these tumors was apparent within 7 days. Total light doses of less than 15 J/cm2 showed no response. Complications of photodynamic therapy, such as intraretinal or subretinal hemorrhages and retinal detachment, were seen only in animals who received total light doses in excess of 43 J/cm2.

Acute ultrastructural changes of cornea after excimer laser ablation.

Corneal ultrastructural changes induced by an argon fluoride excimer laser using different parameters were investigated. Twenty-eight rabbit corneas were ablated at light doses per pulse and repetition rates ranging from 25-800 mJ/cm2 and 1-100 Hz, respectively, at four different total light doses (25-150 J/cm2). Transmission electron microscopy showed that corneal ablations done at subthreshold light doses per pulse with repetition rates higher than 30 Hz and with an exposure more than 100 sec caused significant surface coagulation and an increase in pseudomembrane thickness. These changes were not observed in ablations done above threshold light doses per pulse, regardless of repetition rate and exposure time. However, repetition rates as high as 80 Hz caused damage to the endothelium and Descemet's membrane at the same ablation depth that did not cause such damage using repetition rates under 40 Hz. It appears that high repetition rates used during excimer laser corneal surgery may cause irreversible damage to the cornea.

Ab-interno neodymium:YAG versus erbium:YAG laser sclerostomies in a rabbit model.

This study was undertaken to determine whether thermally-induced tissue necrosis was a factor in ab-interno contact-laser sclerostomy failure. A rabbit model was used to compare the continuous-wave Neodymium (Nd):YAG with the pulsed Erbium (Er):YAG laser with respect to such failure. Laser energy was focused into a fused-silica fiber optic (400 microns) for the Nd:YAG laser (12 W; 3 to 5 seconds), and into a single-crystal, uncladded sapphire fiber optic (250 microns) for the Er:YAG laser (7 to 8 mJ; 250 microseconds; 6 to 8 pulses). The Nd:YAG and Er:YAG lasers required from 21 to 35 J and from 42 to 64 mJ, respectively, to create the sclerostomies. Filtering blebs and intraocular pressure reduction lasted longer (log-rank test; P less than .03) and surgical complications were fewer in the Er:YAG group than in the Nd:YAG group. By creating sclerostomies with minimal thermal damage, the Er:YAG laser may offer significant clinical advantages over lasers producing larger thermal effects.

Subretinal perfluorocarbon liquids. An experimental study.

Perfluorocarbon liquids (PFCL) are fully fluorinated, synthetic, transparent compounds with a high specific gravity. These compounds are being increasingly used as an intraoperative tool for repair of complicated retinal detachments. A known complication of their use, however, is liquid entering the subretinal space via a retinal break. The purpose of this study was to evaluate the effects of two of these liquids when placed subretinally in the rabbit eye. Vitrectomy, retinotomy, and subretinal injection of 0.03 cc of either perfluoroctane, perfluorotributylamine, or balanced salt solution (control eyes) were performed on 36 rabbit eyes. Animals were monitored clinically by indirect ophthalmoscopy and fundus photography for up to 21 days. After the 21-day observation period, electroretinograms (ERG) were taken before the rabbits were killed. Histopathologic studies were done at 3 hours, 24 hours, 3 days, 7 days, 14 days, and 21 days after injection. Three eyes demonstrated tearing of the retinotomy site due to downward migration of the PFCL droplet. Results of the ERGs were normal in all animals tested. Phagocytosis of PFCL droplets by the retinal pigment epithelium (RPE) was observed in 1 eye 3 hours after injection. Three of the eyes that received PFCL injections and all of the control eyes demonstrated moderate intracellular edema of both inner and outer nuclear layers as early as 24 hours after injection. In one eye injected with PFCL, these changes progressed to swelling and cystic formation of the inner nuclear layer and mild degeneration of the outer photoreceptor segments 3 days after injection. It was assumed that these effects occurred on a mechanical basis and were not related to PFCL toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Infrared laser sclerostomies.

Four solid-state lasers with three fiberoptic delivery systems were used to perform laser sclerostomies in an acute-injury rabbit model and in fresh human globes. The lasers used were continuous-wave neodymium:yttrium aluminum garnet (YAG, 1.06 microns) and pulsed holmium:yttrium scandium galliam garnet (YSGG) (2.10 microns), erbium:YSGG (2.79 microns), and erbium:YAG (2.94 microns). Thermal damage to tissue and total laser energy required to produce sclerostomies decreased with increasing wavelength. In human tissue using a 600-microns fused silica fiberoptic, maximum thermal damage (greater than or equal to 100 microns) was noted at 1.06 microns with a total energy of 21 J at a power density of 2.5 kW/cm2. In addition, focal damage to the iris and ciliary body was noted at this wavelength. The least amount of thermal damage (15-20 microns) and lowest total energies needed were found at 2.94 microns. A 250-microseconds pulse length and pulse radiant exposures of 3.6 J/cm2 and 14.3 J/cm2 were used for the low hydroxyl-fused silica (500 microns) and zirconium fluoride (250 microns) fiberoptics, respectively. Although zirconium fluoride fibers have high through-put efficiencies that facilitate study of laser tissue interactions at 2.94 microns, problems encountered with fragility and solubility of the bare tip in aqueous media limit its usefulness. A high attenuation rate with the low hydroxyl-fused silica fiber limited its usable length to 35 cm at 2.94 microns. Tissue damage during sclerostomy formation was minimized at 2.94 microns, reaching a maximum at 1.06 microns. Minimizing tissue damage theoretically could decrease subconjunctival scarring and filtration failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Laser trabecular ablation (LTA).

As part of a pilot study for glaucoma surgery, the use of 3 infrared solid state lasers with 4 fiber optic delivery systems to ablate human trabecular meshwork was investigated. Laser trabecular ablation (LTA) was attempted with the Erbium:YAG (2.94 microns), Erbium:YSGG (2.79 microns), and Holmium:YSGG (2.1 microns) lasers. Laser energy was delivered as a single pulse (250 microseconds) by tissue fiber optic contact with low hydroxyl-fused silica (200 and 500 microns), zirconium fluoride (250 microns), or sapphire (250 microns) fiber optics. Total energy required and thermal effects decreased as laser wavelength increased. LTA was best achieved at 2.94 microns (4 mJ total energy; energy densities = 8.2-12.7 J/cm2; pulse length 250 microseconds) with average thermal damage zones of 5.3-10.3 +/- 1.3-2.4 microns (means +/- SDs) to contiguous structures. This finding has potential applications in the surgical treatment of open-angle and congenital glaucoma and may minimize failure rates seen in other types of surgery on the trabecular meshwork where disrupted trabecular meshwork is not removed.