[Large macular hole-Always a poor prognosis?] / Großes Makulaforamen ­ immer eine schlechte Prognose?

BACKGROUND: Age, preoperative visual acuity and macular hole size have been reported to be prognostic markers for the postoperative outcome in patients with full thickness macular holes (FTMH). OBJECTIVE: A retrospective observational clinical study was performed in order to compare the postoperative course after conventional internal limiting membrane peeling (c-ILM) and inverted flap ILM peeling (i-ILM). Patients with i­ILM peeling had preoperatively a significantly larger macular hole MATERIAL AND METHODS: In this study 45 consecutive patients with a full thickness macular hole (FTMH) were divided into two groups (c-ILM vs. i ILM) and evaluated with respect to the postoperative best corrected visual acuity (BCVA) and retinal morphology. Using spectral domain optical coherence tomography (SD-OCT) the integrity of the outer retinal layers, external limiting membrane (ELM), ellipsoid zone (EZ) and outer photoreceptor outer segments (OS) were analyzed postoperatively for at least 6 months. RESULTS: The preoperative aperture in the i­ILM group was significantly larger (i-ILM = 408.4 µm, SD = 157.5 µm; c­ILM = 287.4 µm, SD = 104.9 µm; p = 0.01). The preoperative BCVA and postoperative BCVA after 1 month were significantly better in the group with c­ILM peeling (p = 0.03 and p = 0.001). The postoperative BCVA after at least 6 months showed no significant difference between the two groups (p = 0.24). The ELM was the first of the outer retinal layers to show postoperative recovery in both groups. CONCLUSION: Using the i­ILM peeling technique in this consecutive series it seemed to be possible to achieve a similar postoperative visual outcome in patients with a large FTMH as for patients with a smaller FTMH operated on with the c­ILM peeling technique.

[Real-time optical coherence tomography-assisted high-precision vitreoretinal surgery in the clinical routine]. / Echtzeit-optische Kohärenztomographie-assistierte Hochpräzisionsvitreoretinalchirurgie in der klinischen Routine.

The complete integration of spectral domain optical coherence tomography (SD-OCT) into an operating microscope now enables targeted, high-resolution imaging-guided vitreoretinal surgery. This provides real-time visualization of retinal layers, vitreous body and instrument-tissue interactions, which can be used for intraoperative decision making. Compared to conventional surgical microscopes, intraoperative OCT enables a greatly enhanced precision of vitreoretinal surgical maneuvers and is an essential prerequisite for the implementation of real-time guided surgical techniques at the micrometer level.

[Vitrectomy and iOCT-assisted inverted ILM flap technique in patients with full thickness macular holes]. / Vitrektomie mit iOCT-assistierter invertierter ILM-Flap-Technik bei großen Makulaforamina.

BACKGROUND: In large full thickness macular holes (FTMH) the closure rate after vitrectomy and conventional internal limiting membrane (ILM) peeling is less than 90%. The aim of this study was to examine the visual acuity and anatomical success rate with high-resolution optical coherence tomography (OCT) after transconjunctival sutureless 23-gauge pars plana vitrectomy as well as intraoperative OCT (iOCT) and Brilliant Peel (BP)-assisted ILM peeling using the inverted ILM flap technique in patients with large FTMHs. METHOD: In this retrospective study 25 eyes of 25 consecutive patients with large FTMH were treated by 23-G vitrectomy with BP and iOCT-assisted ILM peeling using the inverted ILM flap technique followed by gas tamponade. In all patients best corrected visual acuity (BCVA) and the maximum diameter, base and height of the FTMH as well as intraretinal alterations were measured preoperatively using high-resolution spectral domain OCT (SD-OCT, Spectralis, Heidelberg Engineering, Germany). The BCVA was measured after 1, 3, and 6 months. Additionally, the closure rate and the microstructural integrity of the outer retinal layers, e.g. external limiting membrane (ELM), ellipsoid zone und photoreceptor outer segment (OS) were registered in the SD-OCT and correlated with the results of BCVA after macular hole surgery. RESULTS: In all surgical procedures with the inverted ILM flap technique the application of iOCT enabled a good visualization and a controlled positioning of the ILM flaps. At baseline mean BCVA was 0.2 (0.7 logMAR) and improved significantly after 1, 3 und 6 months to 0.4 (0.4 logMAR), 0.5 (0.3 logMAR) and 0.63 (0.2 logMAR), respectively. The closure rate of the FTMHs was 100%. Microstructural integrity of the outer retinal layers was evaluated semiquantitatively and showed good correlation with BCVA. CONCLUSION: Vitrectomy with BP and iOCT-assisted ILM peeling using the inverted ILM flap technique in patients with large FTMH is a very controlled and safe microsurgical strategy and shows good functional and anatomical results. The morphology of the FTMH, the ILM flap and the position of the inverted ILM flap under air was well visualized by IOCT. The microstructural integrity of the outer retinal layers is displayed in detail on SD-OCT and represents an important predictive parameter for BCVA after macular hole surgery.

Elevated day 3 serum follicle stimulating hormone and/or estradiol may predict fetal aneuploidy.

OBJECTIVE: To determine whether baseline serum FSH and/or E2 concentrations can predict the risk for fetal chromosomal abnormalities. DESIGN: Case control study. SETTING: Reproductive technology program at a university hospital. PATIENT(S): Patients who underwent dilation and curettage (D + C), and whose products of conception were karyotyped. INTERVENTION(S): Patients underwent natural conception or controlled ovarian hyperstimulation followed by intrauterine insemination, in vitro fertilization and embryo transfer, gamete intrafallopian transfer, or zygote intrafallopian transfer. MAIN OUTCOME MEASURE(S): Baseline serum FSH and E2 concentrations and fetal karyotype. RESULT(S): Genetic evaluation of 78 D + C specimens revealed 34 normal and 44 abnormal fetal karyotypes. A significantly greater proportion of women with abnormal fetal karyotype had elevated baseline serum FSH (> or =15 mIU/mL [RIA] or 10 mIU/mL [Immulite]) and/or E2 > or = 50 pg/mL [Immulite]) compared with women of normal fetal karyotype. Among karyotypically abnormal abortuses, autosomal trisomy was the most common abnormality noted (79.5%), followed by mosaicism (6.8%), triploidy (6.8%), monosomy XO (4.5%), and balanced translocation (2.3%). CONCLUSION(S): Baseline serum FSH and/or E2 concentrations may be valuable as predictors of fetal aneuploidy.

Genetics, age, and infertility.

OBJECTIVE: To review the genetics of aging specifically as it pertains to human fertility, as well as the recent advancements in the diagnosis of genetic diseases prior to embryo implantation. METHODS: A review of our own experience as well as the scientific literature with regards to the decline in female fertility with age, the success of IVF in women of older reproductive age, and the role of preimplantation genetic diagnosis (PGD) in the evaluation of the patient at risk for fetal genetic anomalies. RESULTS: The decline in female fertility occurs primarily as a result of a decline in oocyte quality as well as quantity. The frequency of chromosomal anomalies in recognized abortuses increases in parallel with the age-specific rise in the incidence of spontaneous abortions. PGD is an accurate diagnostic tool for exclusion of genetically deficient embryos prior to initiation of pregnancy. CONCLUSION: Reproductive failure in women of older age appears to be directly related to ovarian age. Recent techniques such as cytoplasmic or germinal vesicle transfer are designed to replace the senescent cellular machinery believed to be responsible for genetic errors that occur during early cell division. PGD can accurately identify embryos with genetic deficiencies prior to implantation.

Plasma tissue factor pathway inhibitor levels as a marker for postoperative bleeding after enoxaparin use in deep vein thrombosis prophylaxis in orthopedics and general surgery.

Low-molecular-weight heparins (LMWH) are widely used as antithrombotic prophylactic pharmaceutical agents in orthopedic and general surgery. Their antithrombotic characteristics are expressed by plasma mediators such as anti-Xa. anti-IIa, and increased release of tissue factor pathway inhibitor (TFPI) from vascular endothelium. The purpose of this clinical research is to study the relation between plasma levels of these mediators and postoperative bleeding. Forty-one consecutive patients undergoing hip or knee arthroplasty (n = 36) and colectomy (n = 5) received the standard enoxaparin (a LMWH) dose preoperatively (general surgery) or immediately postoperatively (orthopedic surgery). Major bleeding was defined as a postoperative drop of > or = 5 g/dL) of hemoglobin. The authors observed that there was a linear relationship between an increase in free/total TFPI ratio levels and postoperative bleeding. When that ratio increased by >60%, the hemoglobin dropped to >5 g/dL (n = 13). This relationship between free/total TFPI ratio increase and postoperative bleeding was statistically significant (P < 0.001). Those who did not bleed (hemoglobin drop was less than 5 g/dL) (n = 28) had a ratio increase (if any) of less than 50%. However, the authors did not observe any statistical relationship between anti-Xa, anti-IIa, or prothrombin time and postoperative bleeding in patients receiving LMWH for deep vein thrombosis prophylaxis in orthopedic and general surgery patients. The authors recommend a pre- and postoperative ratio level measurement whenever major bleeding is anticipated, as adjustments of LMWH dose or frequency might be necessary.

Plasma tissue factor pathway inhibitor levels as a marker for postoperative bleeding after enoxaparin use in deep vein thrombosis prophylaxis in orthopedics and general surgery.

Low-molecular-weight heparins (LMWH) are widely used as antithrombotic prophylactic pharmaceutical agents in orthopedic and general surgery. Their antithrombotic characteristics are expressed by plasma mediators such as anti-Xa, anti-IIa, and increased release of tissue factor pathway inhibitor (TFPI) from vascular endothelium. The purpose of this clinical research is to study the relation between plasma levels of these mediators and postoperative bleeding. Forty-one consecutive patients undergoing hip or knee arthroplasty (n = 36) and colectomy (n = 5) received the standard enoxaparin (a LMWH) dose preoperatively (general surgery) or immediately postoperatively (orthopedic surgery). Major bleeding was defined as a postoperative drop of > or = 5 g/dL) of hemoglobin. The authors observed that there was a linear relationship between an increase in free/total TFPI ratio levels and postoperative bleeding. When that ratio increased by > 60%, the hemoglobin dropped to > 5 g/dL (n = 17). This relationship between free/total TFPI ratio increase and postoperative bleeding was statistically significant (P < 0.001). Those who did not bleed (hemoglobin drop was less than 5 g/dL) (n = 24) had a ratio increase (if any) of less than 50%. However, the authors did not observe any statistical relationship between anti-Xa, anti-IIa, or prothrombin time and postoperative bleeding in patients receiving LMWH for deep vein thrombosis prophylaxis in orthopedic and general surgery patients. The authors recommend a pre- and postoperative ratio level measurement whenever major bleeding is anticipated, as adjustments of LMWH dose or frequency might be necessary.

Relationship between alpha 2-adrenergic receptor binding sites and the functional receptors inhibiting norepinephrine release in rat cerebral cortex.

The properties of alpha 2-adrenergic receptor binding sites and the receptors inhibiting [3H]norepinephrine (3H-NE) release from slices of cerebral cortex were compared. [3H]RX 781094, an alpha 2-adrenergic receptor antagonist radioligand, labeled a single class of binding sites in membranes at 37 degrees with the pharmacological specificity expected of alpha 2-adrenergic receptors. 5'-Guanylimidodiphosphate (Gpp(NH)p) and NaCl caused small increases in the potencies of antagonists at the 3H-RX binding sites but decreased the potencies of agonists 4-22-fold. Antagonists blocked the inhibition of potassium-evoked 3H-NE release caused by exogenous NE with potencies similar to those in competing for 3H-RX binding sites. Partial receptor inactivation with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was used to determine whether there was a receptor reserve. EEDQ dose-dependently decreased both the density of 3H-RX binding sites and the maximal inhibition of 3H-NE release by different agonists. For most agonists, KA values calculated after the receptor inactivation did not differ significantly from EC50 values; however, for epinephrine a small receptor reserve was apparent. The proportion of 3H-RX binding sites lost was similar to the proportion of functional receptors lost after EEDQ treatment. The functional KA values for agonists correlated most closely with KD values for the low affinity binding state observed in the presence of Gpp(NH)p and NaCl. However, both epinephrine and NE still showed two-site binding curves under these conditions, and it was the high affinity subpopulation of sites observed in the presence of Gpp(NH)p and NaCl which resembled most closely the functional KA values. These data suggest that 3H-RX labels binding sites with properties similar to the alpha 2-adrenergic receptors inhibiting 3H-NE release in cerebral cortex. There is little or no receptor reserve for this effect, and there appears to be a binding state for the natural catecholamine agonists which has an affinity lower than that for mediating this functional response.

Minimal access surgery in gynecologic cancer: we can, but should we?

Operative laparoscopists continue to refine surgical techniques applicable to patients with gynecologic malignancies. Various techniques for radical hysterectomy and larger series of patients with endometrial cancer have now been reported. The technical feasibility of such operations is being established. Although oncologic patients may enjoy the known benefits of laparoscopic surgery, such as shorter hospitalization, the known shortcomings, such as longer operative times and increased cost, are a concern. The unknown shortcomings and the unknown overall survival of laparoscopically managed patients continue to keep the majority of oncologic surgeons a safe distance away.

Laparoscopic management of suspicious adnexal masses.

OBJECTIVE: Our aim was to evaluate the feasibility and applicability of operative laparoscopy in the management of adnexal masses that do not meet the standard serum CA 125 and ultrasonographic criteria for benignity. STUDY DESIGN: One hundred thirty-eight patients underwent operative laparoscopy for removal of suspicious adnexal masses. The CA 125 level was > 35 mlU/ml in 39 of 138 (28%) patients; ultrasonographic findings were abnormal in 127 of 138 (92%); masses were > 10 cm in 43 of 138 (32%) of patients. RESULTS: Malignancies were discovered in 14% (19/138) of patients. Eight percent (11/138) of the procedures were converted to laparotomy, six because of inability to dissect the mass laparoscopically and five for staging or debulking of carcinoma. Operative times ranged from 25 to 210 minutes, with a mean of 86. Three major complications were encountered-an enterotomy and a lacerated vena cava, both of which were repaired laparoscopically, and a small bowel herniation through a lateral port site that required reoperation. Hospital stays ranged from 0 to 11 days, with a mean of 1.5. In two patients with "apparent" stage I adnexal carcinomas recurrence was diagnosed 6 and 38 months after surgery. CONCLUSIONS: Laparoscopic management of suspicious adnexal masses is technically feasible, with a low rate of morbidity and a short hospital stay. Adnexal carcinomas can be identified and managed appropriately with staging and complete resection as indicated.

Three-dimensional measurement of gestational and yolk sac volumes as predictors of pregnancy outcome in the first trimester.

Along with crown-rump length (CRL), the size (diameter) of embryonic structures such as gestational sac (GS) and yolk sac (YS) may have prognostic value for embryonic development. We proposed that first-trimester volume calculations of these structures using transvaginal three-dimensional ultrasound technique may have value as predictors of adverse reproductive outcome. Forty-nine consecutive patients (treated for infertility) with singleton pregnancies were included in this prospective study. Seventy-three examinations were performed in case of pregnancies with normal, and 12 with abnormal outcome. GS and YS volumes were plotted against gestational age (GA) (25-65 days post ovulation) to create nomograms for normal outcome and the same procedure was carried out with CRL measurements as well. Measurements of abnormal pregnancies were compared with these nomograms. Specificity, sensitivity, positive and negative predictive values were also calculated. Regression analysis revealed a power correlation between GS volumes and GA, logarithmic relationship was observed when YS volumes were plotted against GA. CRL showed logarithmic correlation with GA as well. Both GS volumetry and CRL measurements proved to have statistically significant predictive value for adverse outcome (p<0.05). However, no statistically significant difference was found when YS volumes of normal and abnormal pregnancies were compared. Specificity, sensitivity, positive and negative predictive values of GS volumes and CRL were similar. Mean YS/GS ratios also had good predictive values (p<0.05). Volume determination of YS and GS can be performed quickly and simply applying three-dimensional sonography. Volumetry of GS proved to be a sensitive predictor for pregnancy outcome and can be a good supplement to CRL measurements.

Reserpine-induced postjunctional supersensitivity in rat vas deferens and caudal artery without changes in alpha adrenergic receptors.

Caudal artery and vas deferens from rats treated chronically with reserpine (1 mg/kg/day i.p.) were used to study drug-induced postjunctional supersensitivity in smooth muscle. There was no change in contractile sensitivity of the rat vas deferens after 1 day of reserpine treatment; however, there were similar increases in sensitivity 4 and 7 days after reserpine treatment. The potencies of phenylephrine, methacholine and potassium chloride in causing contraction of the vas deferens were significantly increased by 4.9-, 19.5- and 1.23-fold, respectively, after 7 days of chronic treatment. This treatment also increased the potencies of phenylephrine, serotonin and potassium chloride in causing contraction of rat caudal artery by 1.8-, 1.7- and 1.23-fold, respectively; however, the potency of clonidine was unchanged after 7 days of reserpine treatment. There was no change in sensitivity to phenylephrine 1 day after reserpine treatment but sensitivity was significantly increased after 4 days. There was no significant change in maximum contractile response in either tissue to any of these agents after chronic reserpine treatment. Scatchard analysis of saturation isotherms of specific [125I]BE 2254 binding to membrane fractions from rat vas deferens and caudal artery showed no change in the density or affinity of alpha-1 adrenergic receptors after 1, 4 or 7 days of chronic reserpine treatment. In addition, no change was observed in specific [3H]rauwolscine binding to either tissue after 7 days of chronic reserpine treatment, suggesting no change in alpha-2 adrenergic receptors. These data indicate that changes in alpha adrenergic receptors are not involved in postjunctional supersensitivity of smooth muscle caused by chronic reserpine treatment.

Accuracy of residual urine measurement in men: comparison between real-time ultrasonography and catheterization.

PURPOSE: The practical value of ultrasonography as a rapid means to determine accurately residual urine volume was assessed. MATERIALS AND METHODS: Transverse and sagittal bladder diameters, as well as areas from longitudinal and transverse images, were measured with real-time ultrasonography in 324 men immediately after voiding. Calculated bladder volumes using measured diameters and areas for each of 11 formulas in the literature were compared to the corresponding measured total residual urine volumes. RESULTS: The lower limit of ultrasonographic visualization of urine in the bladder was approximately 48 ml. No correlation existed between ultrasound calculated bladder volumes and measured residual urine for any of the 11 formulas. CONCLUSIONS: Ultrasonography cannot rapidly measure bladder volumes accurately to date. Catheterization remains the most accurate method of assessing post-void residuals but in many cases it may not be the best approach to patient care.

Novel phosphonium salts display in vitro and in vivo cytotoxic activity against human ovarian cancer cell lines.

Phosphonium salts are part of a class of lipophilic cationic molecules that accumulate preferentially in mitochondria and inhibit the growth of human and rodent carcinoma cells in vitro and in animal models. The delocalized cations tested previously such as dequalinium have exhibited considerable cross resistance against multiple drug-resistant cells expressing gp 170. In order to overcome this cross resistance, we have developed two novel phosphonium salts which contain haloalkyl moieties with potential protein alkylating capabilities. 3-Chloropropyltris(4-dimethylaminophenyl)phosphonium chloride (APPCL) and 3-iodopropyltris(4-dimethylaminophenyl)phosphonium iodide (APPI) are more lipophilic than other phosphonium salts described to date. By comparing the 50% inhibitory concentration (IC50) values for the A2780 human ovarian carcinoma parental line to a multiple drug-resistant variant (A2780-DR), the degree of cross resistance (IC50 for A2780-DR/IC50 for A2780 Parental) were found to be 494 for doxorubicin, but only 2.7 for APPCL. Similarly, the degree of cross resistance using a cisplatin-resistant variant (IC50 for A2780-CR/IC50 for A2780 Parental) was 30 for cisplatin, but only 2.2 for APPCL. APPCL is also active in vitro against UCI 101 (IC50 = 80 nM), an ovarian carcinoma line isolated from a patient who had failed chemotherapy with taxol, doxorubicin, and high-dose cisplatin. The cytotoxicity of APPI was comparable to that of APPCL with an IC50 ranging from 16.7 to 83.0 nM for a panel of seven cell lines. When administered intraperitoneally at a total dose of 46 mg/kg over 15 days, APPCL increased the median lifespan of nude mice bearing UCI 101, from a control value of 48.0 to 92.5 days (P < 0.0061). The median survival of the APPI-treated mice was 55 days. A total of 37.5% of the APPCL-treated group and 12.5% of the APPI-treated group were long-term survivors: sacrifice of these mice on Day 180 and subsequent histology showed no evidence of disease. Exposure to APPCL and APPI caused mitochondrial damage to UCI 101 cells at sublethal doses in vitro, as shown by morphological damage observed with transmission electron microscopy. APPCL appears to decrease the uptake of rhodamine 123 by mitochondria, suggesting that mitochondria may be significant targets or initial reservoirs for this agent. In conclusion, APPI and APPCL show promising anticancer activity against a variety of human ovarian carcinoma cell lines warranting further investigation.