Ultrasound biomicroscopic examination of acute hydrops in patients with keratoconus

PURPOSE: To investigate the possible factors involved in the development of acute hydrops in patients with keratoconus. DESIGN: Prospective interventional case series. METHODS: Thirteen consecutive keratoconic eyes of 13 patients with acute hydrops were examined by ultrasound biomicroscopy (UBM). RESULTS: Ultrasound biomicroscopy (UBM) examinations revealed a rupture of Descemet membrane and intrastromal clefts in all eyes. In 11 of 13 eyes, the intrastromal clefts were connected to the anterior chamber. CONCLUSIONS: Formation of intrastromal clefts may be an important factor in the development of acute hydrops in keratoconic eyes. The clefts may cause severe corneal edema and delay the closure of Descemet membrane during the resolution of corneal edema.     

Pulsation in polypoidal choroidal vasculopathy

PURPOSE: To evaluate the relationship between pulsation and the fundus lesion in polypoidal choroidal vasculopathy (PCV). OBJECTIVE AND METHODS: We studied 26 eyes with PCV by indocyanine green angiography (IA) with a heidelberg retina angiograph(HRA). The 26 eyes were classified into two groups; pulsatile PCV and non-pulsatile PCV. We evaluated the strength and the amplitude of the pulsation, and the frequency of subretinal hemorrhage within one year after the first IA. Seven eyes in the pulsatile PCV group were tested by HRA twice or more to evaluate the relationship between the fundus lesion and the change in the strength and the amplitude of pulsation. RESULTS: Subretinal hemorrhage occurred in 9 of 14 eyes with pulsatile PCV and in 2 of 12 eyes with non-pulsatile PCV (odds ratio : 12.5). The possibility of subretinal hemorrhage was significantly higher in pulsatile PCV than in non-pulsatile PCV. In 3 of the 7 eyes tested twice or more, the fundus lesion worsened as the pulsation strengthened and the area of pulsation enlarged. In 1 of the 7 eyes, the fundus lesion improved as the pulsation weakened and the area of pulsation decreased. CONCLUSION: There is a good possibility that strengthened and extended pulsation is related to increasing subretinal hemorrhage in PCV patients.     

Effect of Prostaglandin E1 on Ischemia–Reperfusion Injury During Abdominal Aortic Aneurysm Surgery

Objective Abdominal aortic aneurysm (AAA) surgery subjects the lower extremities to ischemia and reperfusion. Although it is not extensive or prolonged, ischemia of the lower extremities during aortic cross-clamping is gradually and steadily induced. We studied the effects of prostaglandin E₁ (PGE₁) on ischemia–reperfusion injury of the lower extremities during AAA repair. Methods During AAA surgery, two near-infrared spectroscopy probes were positioned on each calf muscle to monitor oxygen metabolism in the lower extremities. We also measured lactate concentration in both iliac veins. Results Near-infrared spectroscopy signals responded sensitively to aortic cross-clamping and declamping. Lactate increased time-dependently during aortic cross-clamping. The continuous venous administration of PGE₁ (20 ng/kg per minute) inhibited the accumulation of lactate during aortic cross-clamping. Declamping of the first iliac artery resulted in a further but transient increase in ipsilateral venous lactate, which may be one component in the mechanism of declamping shock. Prostaglandin E₁ eliminated the transient increase in ipsilateral lactate. The administration of PGE₁ inhibited the contralateral accumulation of lactate after first declamping, and the lactate level decreased gradually before the second declamping. Conclusions Prostaglandin E₁ seems to have a protective effect against ischemia–reperfusion injury of the lower extremities during AAA surgery.     

Compartment Syndrome of Bilateral Lower Extremities Following Laparoscopic Surgery of Rectal Cancer in Lithotomy Position: Report of a Case

A 67-year-old man underwent laparoscopic surgery for rectal cancer in the lithotomy position. After surgery he complained of bilateral lower limb pain, swollen legs, and sensory disturbance. The serum creatine kinase value was 46 662 U/l. Venography demonstrated compression from outside without any obstruction. The T2 image of magnetic resonance imaging (MRI) showed a massive swollen muscle and a partial high-intensity area in the bilateral lower limbs. The posterior compartment pressures of lower legs were high (gastrocnemius muscle: 30 mmHg [right] and 44 mmHg [left]). Compartment syndrome (superficial posterior compartment) was thus diagnosed. He underwent a fasciotomy using the single dorsal approach and the administration of a large amount of fluid. He recovered well without any motor or sensory deficits. Compartment syndrome is rare, occurring only once in every 3500 cases, but it is a severe complication of surgery in the lithotomy position. Several risk factors have been pointed out: including prolonged operation, hardness of the operating table, obesity, dehydration, and hypothermia. To prevent compartment syndrome, appropriate positioning during surgery is therefore essential. To make a timely diagnosis and identify the precise location of muscle edema, the T2 image of MRI is useful.     

Inter/intra investigator variation in orchidometric measurements of testicular volume by ten investigators from five institutions

Aim： To perform quality control studies on testicular volume measurements for a multi-center epidemiological study of male reproductive function. Methods： We constructed a data matrix with a balanced assignment for 2 consecutive days by ten investigators （andrological career： 4-21 years） from five institutions and 12 male volunteers aged 20-26 years. Testicular volume was measured by Prader＇s orchidometer. A skilled technician also performed an ultrasound estimate of testicular volume. Results： A statistically significant inter-investigator variation was found for both testes （P 〈 0.05）. In addition, there was a statistically significant investigator-by-volunteer interaction in testicular volume measurement （P 〈 0.01）. However, there was no statistically significant difference in the two measurements performed on consecutive days for either testis. The testicular volumes for both the right and left testes as estimated by ultrasonography were smaller than results using the orchidometer. However, there was no statistical significance （P 〉 0.05）. The difference in experiences of the investigators did not significantly correlate with accuracy of measurements in either testis. Conclusion： The present study revealed significant differences in the results of estimation of testicular volume among the ten investigators, but intra-investigator variation was not considerable. Improved training and proper standardization of the measurement will be necessary before starting a multi-center study based on an andrological examination.     

A study of the xenoantigenicity of neonatal porcine islet-like cell clusters (NPCC) and the efficiency of adenovirus-mediated DAF (CD55) expression

BACKGROUND: The pig pancreas is considered to be the most suitable source of islets for xenotransplantation in patients with type I diabetes. The objective of this study was to assess the antigenicity of neonatal porcine islet-like cell clusters (NPCC), including the Galalpha1-3Galbeta1-4GlcNAc-R (alpha-Gal) and Hanganutziu-Deicher (H-D) antigens, and the pathway involved in human complement activation. The efficiency of expression of human decay-accelerating factor (DAF: CD55) on NPCC by adenoviral transduction was also examined, and the functional capacity of DAF was also estimated. METHODS: The deposition of human natural antibodies, immunoglobulin (Ig)G and IgM, and the expression of alpha-Gal and H-D antigens on NPCC were investigated by FACS analysis. The downregulation in the antigenicity to human natural antibodies, including the alpha-Gal and H-D antigens on NPCC by treatment with tunicamycin, PDMP and neuraminidase were also examined. In addition, complement-mediated islet lysis was examined using factor D-deficient and C1-deficient sera. An adenovirus encoding DAF under the control of the cytomegalovirus promoter, Ad.pCMV-DAF, was then constructed, and used for transducing NPCC. The amelioration of complement-dependent cytotoxicity of the NPCC by the transduced DAF was assessed as an in vitro hyperacute rejection model of a pig to human xenograft. RESULTS: The NPCC clearly expressed the alpha-Gal epitope, and the human natural antibodies, IgG and IgM, and the anti-H-D antibody also reacted with the NPCC. Treatment of NPCC with tunicamycin led to a drastic reduction in the extent of deposition of IgG, indicating the importance of N-linked sugars on the islets, presumably related to alpha-Gal expression on N-linked sugars. Neuraminidase treatment indicated the presence of, not only the H-D antigen, but also other sialic acid antigens which reacted with the human natural antibody, especially IgG. The complement deposition of factor B on NPCC was clear, and the alternative pathway-mediated NPCC killing accounted for approximately 30% of that by the total complement pathway. On the other hand, approximately 90% of the NPCC could be transduced to express DAF by the adenovector, Ad.pCMV-DAF. The expressed DAF showed an approximately 50-62% suppression in complement-dependent NPCC lysis. CONCLUSION: The origin of the antigenicity of NPCC is mainly N-linked sugars including alpha-Gal and sialic acid antigens, and NPCC expressed the transduced molecule in high efficiency by the adenovector.     

A novel strategy for preventing human CD8+ cytotoxic T lymphocyte-mediated cytotoxicity against pig endothelial cells by overexpression of pig cellular FLICE-like inhibitory protein (c-FLIP) gene

Human CD8+ cytotoxic T lymphocyte (CTL)-mediated cytotoxicity in xenograft recipients is an important obstacle for successful xenotransplantation of pig organs into humans. In our previous study, we demonstrated that xenocytotoxicity of human CD8+ CTL detrimental to pig endothelial cells (PEC) is mediated mainly by the Fas/FasL apoptotic pathway. Furthermore, we developed new methods to prevent this CTL killing by extracellular remodeling using overexpression of human decoy Fas antigen and membrane-bound human FasL on pig xenograft cells. The cellular FLICE-inhibitory protein (c-FLIP), a caspase-8 inhibitor that lacks the cysteine domain, is a negative regulator of death receptor-mediated apoptosis. c-FLIP proteins exist as long (c-FLIP(L)) and short (c-FLIPs) splice variants, both capable of protecting cells from death receptor-mediated apoptosis. In this report, we have demonstrated that both pig c-FLIPs and pig c-FLIP(L) significantly inhibit human CD8+ CTL-mediated xenocytotoxicity toward stably transfected PEC, although the expression level of pig Fas antigen on cell surface was not changed. These data suggested that intracellular remodeling with overexpression of pig c-FLIP in xenograft cells may decrease the innate cellular responses against xenografts, facilitating long-term xenograft survival.