Significant correlations between photopic negative response,afferent pupillary defect,and mean defects of visual fields in asymmetric optic nerve disorders

Purpose

The photopic negative response (PhNR) is a negative wave following the b-wave of the photopic electroretinogram (ERG). The PhNR originates from the retinal ganglion cells (RGCs), and it can be used to assess the function of RGCs noninvasively and objectively. The purpose of this study was to determine whether the relative amplitudes (affected/normal eye) of the PhNR are significantly correlated with the degree of the relative afferent pupillary defect (RAPD) in eyes with unilateral or asymmetrical damage of the optic nerve.

Methods

The PhNRs of the full-field photopic ERGs were measured. In addition, videopupillography and automated perimetry were performed on 27 cases with asymmetrical optic nerve disorders including glaucoma. The differences of these assessments were expressed by the relative amplitudes of the PhNRs of the two eyes, the neutral density (ND) filter required to equate the amplitudes of the pupillary light reflexes between the two eyes, and differences of the mean defects (ΔMDs) of the sensitivities of the Humphrey visual fields. The correlations between these values were determined by linear regression analyses.

Results

The relative PhNR amplitudes were significantly and negatively correlated with the ΔMDs (R² = 0.58, P = 0.0001). In addition, the relative PhNR amplitudes were moderately but significantly and positively correlated with the RAPDs (R² = 0.36, P = 0.002).

Conclusion

The relative amplitudes of the PhNR of the affected eyes to the contralateral eyes indicate an asymmetric alteration of the RGCs, and they can be used to monitor the physiology of the RGCs objectively.

     

Dietary l-Lysine Prevents Arterial Calcification in Adenine-Induced Uremic Rats

Vascular calcification (VC) is a life-threatening complication of CKD. Severe protein restriction causes a shortage of essential amino acids, and exacerbates VC in rats. Therefore, we investigated the effects of dietary l-lysine, the first-limiting amino acid of cereal grains, on VC. Male Sprague-Dawley rats at age 13 weeks were divided randomly into four groups: low-protein (LP) diet (group LP), LP diet+adenine (group Ade), LP diet+adenine+glycine (group Gly) as a control amino acid group, and LP diet+adenine+l-lysine·HCl (group Lys). At age 18 weeks, group LP had no VC, whereas groups Ade and Gly had comparable levels of severe VC. l-Lysine supplementation almost completely ameliorated VC. Physical parameters and serum creatinine, urea nitrogen, and phosphate did not differ among groups Ade, Gly, and Lys. Notably, serum calcium in group Lys was slightly but significantly higher than in groups Ade and Gly. Dietary l-lysine strongly suppressed plasma intact parathyroid hormone in adenine rats and supported a proper bone-vascular axis. The conserved orientation of the femoral apatite in group Lys also evidenced the bone-protective effects of l-lysine. Dietary l-lysine elevated plasma alanine, proline, arginine, and homoarginine but not lysine. Analyses in vitro demonstrated that alanine and proline inhibit apoptosis of cultured vascular smooth muscle cells, and that arginine and homoarginine attenuate mineral precipitations in a supersaturated calcium/phosphate solution. In conclusion, dietary supplementation of l-lysine ameliorated VC by modifying key pathways that exacerbate VC.Medial vascular calcification is common in aging, diabetes, and CKD.^1–4 Because the presence of vascular calcification is strongly associated with increased cardiovascular morbidity and mortality, several studies in both animals and humans have sought ways to reduce the extent of vascular calcification.^5–10 However, satisfactory therapies have not yet been established.¹¹Adenine-induced renal failure is one of the commonly used animal models for studying the development of vascular calcification, but the prevalence of vascular calcification in this model is not very high. Indeed, Price et al. reported that vascular calcification was detected in only 30% of rats with adenine-induced chronic renal failure (adenine rats) fed a normal-protein diet.⁵ These authors speculated that consistent vascular calcification might require a longer period of adenine feeding. On the basis of this idea, they designed a low-protein (LP) diet in an attempt to reduce the nitrogen load and thus enable the rats to thrive on the adenine diet for longer periods. As a result of this attempt, Price et al. unexpectedly found that adenine rats fed a LP diet had extensive vascular calcification without a longer feeding period.⁵ All 13 adenine rats fed the LP diet had uniform alizarin red staining of the aorta, whereas only 3 of the 11 adenine rats fed a normal-protein diet had partial calcification.⁵ These findings indicated that dietary protein deficiency correlates with the extent of vascular calcification.Proteins are usually made from 20 kinds of amino acids. On the basis of nutritional requirements, these amino acids can be divided into two groups: essential amino acids (EAAs) and non-EAAs. Because restriction of dietary protein results in a shortage of EAAs, the level of dietary EAAs may be relevant to the extent of vascular calcification. Among nine EAAs, this study focused on l-lysine (l-Lys) based on the following three reasons. First, l-Lys is the first-limiting amino acid in most cereal grains.¹² Second, the safety of l-Lys supplementation has been verified in the area of animal husbandry. l-Lys has long been added to feed grains in order to improve the utility of feed proteins.¹³ Third, several studies have demonstrated that dietary supplementation with l-Lys protects bones from osteoporosis, a pathologic condition that often coexists with vascular calcification.^14,15 These points prompted us to hypothesize that supplementation with l-Lys would ameliorate vascular calcification. Therefore, in this study, we tested this hypothesis using adenine rats.     

Use of prostaglandin I2 analog in treatment of massive hepatic necrosis associated with endothelial cell injury and diffuse sinusoidal fibrin deposition

Endothelial cell damage causes massive hepatic necrosis as a result of fibrin deposition in the hepatic sinusoids. When a stable analog of prostaglandin I₂, beraprost sodium, was administered to rats given either dimethylnitrosamine, carbon tetrachloride, or endotoxin followingCorynebacterium parvum administration, the hepatic necrosis produced in each was attenuated, but to a greater extent in the dimethylnitrosamine and endotoxin/Corynebacterium parvum models, where fibrin deposition in the hepatic sinusoids occurs, as compared to the carbon tetrachloride model, where such fibrin deposition does not occur. Beraprost sodium reduced the expected increase of portal venous pressure in the endotoxin/Corynebacterium parvum model without affecting plasma thrombin-antithrombin III complex levels. Beraprost sodium also significantly reduced cell killing of both isolated rat hepatocytes and hepatic sinusoidal endothelial cells exposed totert-butyl hydroperoxide when compared to controls. Beraprost sodium could prove to be a therapeutic candidate for the treatment of hepatic necrosis, particularly in cases associated with fibrin deposition in the hepatic sinusoids because of its fibrin clot-clearning action.     

Hereditary hemorrhagic telangiectasia with growing pulmonary arteriovenous fistulas followed for 24 years

A 47-year-old man was admitted for follow-up of an abnormal chest x-ray. He had a history of epistaxis and a brain abscess and a family history of pulmonary arteriovenous fistulas. Physical examination showed clubbed fingers and telangiectasia of the tongue. Laboratory data revealed evidence of polycythemia and hypoxia. Contrast echocardiography and pulmonary perfusion scintigraphy were suggestive of a right-to-left shunt. From the oxygen tension and content of blood taken at cardiac catheterization, the shunt ratio was calculated to be 57.8%. Multiple bilateral pulmonary arteriovenous fistulas were confirmed by angiography, and the patient was diagnosed as having hereditary hemorrhagic telangiectasia. A review of x-ray films taken over a 24-year period demonstrated that the fistulas in both lungs had been increasing gradually in size at different rates. A right lower lobectomy relieved the hypoxia, but the patient died unexpectedly on the twelfth postoperative day. There was no evidence of fistula rupture on chest film, but no autopsy was performed.     

Effects of the antioxidative beta-blocker celiprolol on endothelial progenitor cells in hypertensive rats

BackgroundEndothelial progenitor cells (EPCs) derived from bone marrow migrate to areas of endothelial damage and repair them. EPC function is impaired by oxidative stress. We examined the effects of an antioxidative beta(1)-adrenoceptor blocker on the number and function of EPCs in hypertensive rats.MethodsSpontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were fed diets loaded with high salt. The SHRs were treated with celiprolol or atenolol for 2 weeks. Peripheral blood mononuclear cells (MNCs) were separated, subjected to flow cytometric analysis to determine the number of circulating EPCs, and cultured to quantify EPC colony formation. EPC migration was evaluated in migration assay chambers. EPC senescence was evaluated using beta-galactosidase assay. Oxidative stress of EPCs was evaluated using thiobarbituric acid-reactive substance (TBARS) assay. The expression of nicotinamine adenine dinucleotide phosphate (NAD(P)H) oxidase component mRNAs in the renal cortex, aorta, and heart were evaluated by real-time PCR.ResultsThe number, colony formation, and migration of EPCs in SHRs were significantly lower than those in WKY rats. TBARS scores in EPCs from SHRs were significantly higher than those from WKY rats. Celiprolol increased the number of circulating EPCs and stimulated EPC colony formation and migration, while decreasing EPC senescence. Celiprolol inhibited oxidation in EPCs from SHRs, and decreased the expression of NAD(P)H oxidase component mRNAs in the renal cortex, aorta, and heart.ConclusionEPCs are impaired in SHRs in response to oxidative stress. Celiprolol decreases oxidative stress in hypertension in vivo and improves EPC numbers and function. It appears, therefore, that celiprolol may exert beneficial cardiovascular effects through its antioxidative properties.American Journal of Hypertension (2008). doi 10.1038/ajh.2008.233American Journal of Hypertension (2008); 21, 9, 1062-1068. doi 10.1038/ajh.2008.233.     

Long-term follow-up of transvenous defibrillation leads: high incidence of fracture in coaxial polyurethane lead.

BACKGROUND: As a result of longer follow-up after implantation of cardioverter defibrillators (ICD), fatigue of the leads has become a concern. The aim of this study was to determine the incidence and clinical presentation of ICD lead failures. METHODS AND RESULTS: The study population consisted of 241 patients with 249 ICD leads who underwent implantation of an ICD with a transvenous lead system. After device implantation, the patients were routinely followed up every 4 months. Five lead failures (2.0%) occurred as an oversensing of artifact during the follow-up period (2.6+/-2.1 years); 4 of those 5 patients received inappropriate shocks and 1 case of lead failure was identified in a patient with frequent episodes of non-sustained ventricular fibrillation. In particular, the right ventricular polyurethane transvenous lead in the Medtronic model 6936 failed in 4 (13%) of 31 cases. Percutaneous lead extraction was not available in all cases, so an additional ICD lead was inserted through the same site of the subclavian vein. CONCLUSIONS: Lead failures may occur 5 years after ICD implantation and polyurethane leads have an especially high incidence of failure. However, there were no follow-up parameters observed that predicted lead failures.     

A Case of Extragenital Choriocarcinoma in the Jejunum

A case of extragenital choriocarcinoma which produces human chorionic gonadotropin (HCG) in the small intestine of a 48-yr-old Japanese women is reported. Only seven such cases have been reported. The patient complained of postprandial upper abdominal pain and vomiting of 5 months' duration. Nine years before, right upper lobectomy was performed because of lung undifferentiated carcinoma. Double-contrast examination of the small intestine showed irregular ulceration in the lower jejunum. Celiac angiography demonstrated a hypervascular tumor stain in the branch of the jejunal artery. The serum HCG level was elevated. Gynecological examination revealed nothing abnormal. A small intestinal neoplasm was diagnosed, and a partial resection of the jejunum was performed. Endoscopy on the operating table showed a large, irregularly shaped sessile ulcer. Histologically the tumor was diagnosed as choriocarcinoma, composed of syncytiotrophoblastic cells and cytotrophoblastic cells. Immunohistochemical staining for HCG was positive. No metastasis was present. Although extragenital choriocarcinoma in the small intestine is rare, it should be included in the differential diagnosis of small intestinal neoplasm.     

Comparative analysis of different enzyme immunoassays for assessment of phosphatidylserine-dependent antiprothrombin antibodies

Phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) were strongly correlated with the presence of lupus anticoagulant showing a high specificity for the diagnosis of antiphospholipid syndrome. However, the main criticism for the clinical applicability of aPS/PT testing is the lack of reproducibility of the results among laboratories. In this study, we measured IgG and IgM aPS/PT using our original in-house enzyme-linked immunosorbent assays (ELISA) and commercial ELISA kits to assess the assay performance and to evaluate the accuracy of aPS/PT results. The study included 111 plasma samples collected from patients and stored at our laboratory for aPS/PT assessment. Sixty-one samples were tested for IgG aPS/PT using two assays: (1) aPS/PT in-house ELISA and (2) QUANTA Lite? aPS/PT IgG ELISA kit (INOVA Diagnostics, Inc., USA). Fifty samples were evaluated for IgM aPS/PT using two assays: (1) aPS/PT in-house ELISA and (2) QUANTA Lite? aPS/PT IgM ELISA kit (INOVA Diagnostics). Ninety-eight percent of samples yielded concordant results for IgG aPS/PT and 82 % for IgM aPS/PT. There was an excellent agreement between the IgG aPS/PT assays (Cohen κ = 0.962) and moderate agreement between the IgM aPS/PT assays (κ = 0.597). Statistically significant correlations in the aPS/PT results were obtained from both IgG and IgM aPS/PT assays (r = 0.749, r = 0.622, p < 0.001, respectively). In conclusion, IgG and IgM detection by ELISA is accurate. The performance of aPS/PT is reliable, and concordant results can be obtained using different ELISA methods.