SS-MIX: a ministry project to promote standardized healthcare information exchange.

OBJECTIVES: To promote healthcare information exchange between providers and to allow hospital information systems (HIS) export information in standardized format (HL7 and DICOM) in an environment of wide-spread legacy systems, which only can export data in proprietary format. METHODS: Through the Shizuoka prefecture EMR project in 2004-2005, followed by the ministry's SS-MIX project, many software products have been provided, which consist of 1) a standardized storage to receive HL7 v2.5 messages of patient demographics, prescription orders, laboratory results, and diagnostic disease in ICD-10, 2) a referral letter creation system, 3) a formatted document creation system, 4) a progress note/nursing record system, and 5) an archive/viewer to incorporate incoming healthcare data CD and allow users to view on HIS terminal. Meanwhile, other useful applications have been produced, such as adverse event reporting and clinical information retrieval. To achieve the above-mentioned objectives, these software products were created and propagated, because users can use these software products, provided that their HIS can export the above information to the standardized storage in HL7 v2.5 format. RESULTS: In 20 hospitals of Japan, the standardized storage has been installed and some applications have been used. As major HIS vendors are shipping HIS with HL7 export function since 2007, HIS of 594 hospitals in Japan became capable of exporting data in HL7 v2.5 format (as of March 2010). CONCLUSIONS: In high CPOE installation rate (85% in 400+ bed hospitals), though most of them only capable of exporting data in proprietary format, prefecture and ministry projects were effective to promote healthcare information exchange between providers. The standardized storage became an infrastructure for many useful applications, and many hospitals started using them. Ministry designation of proposed healthcare standards was effective so as to allow vendors to conform their products, and users to install them.

[Endogenous substance P in corneal epithelial cells and keratocytes].

PURPOSE: To detect endogenous substance P(SP) and neurokinin receptor 1(NK1R) in cultured human epithelial cells of the cornea(HE) and human keratocytes(HK). METHOD: Messenger RNA(mRNA) expression of SP and endogenous SP in HE and HK were detected by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). mRNA expression of NK1R in HE and HK was detected by RT-PCR. RESULTS: The mRNA expression of SP and endogenous SP were recognized in HE and HK. The mRNA of NK1R was also expressed in HE and HK. CONCLUSION: It appears that endogenous SP regulates the biological functions of HE and HK in an autocrine or paracrine fashion.

Internal echo histogram examination has a role in distinguishing malignant tumors from benign masses in the breast.

We analyzed the histograms of reflecting ultrasound (US) from the internal areas of the masses of 50 lesions in the breast. The central average of gravity and the ratio between lower and higher width in the histograms were compared as the parameters. Statistical significance were found in both parameters between malignant tumors and benign masses (P<.001, P<.01). Therefore, analysis of histograms based on reflecting US was useful in making differential diagnoses of malignant tumors and benign masses in the breast.

Corneal dystrophies in Japan.

Recent advances in molecular genetics have increased our understanding of the role of genes. Four autosomal dominant corneal dystrophies (CDs); granular CD (GCD), Avellino CD (ACD), lattice CD (LCD), and Reis-Bücklers CD (RBCD) were mapped to the long arm of chromosome 5 (5q31). These four diseases were shown, in a Caucasian series, to result from different missense mutations in the TGFBI (BIGH3, keratoepithelin) gene. The same mutations were also detected in Japanese patients, from a different ethnic background. Gelatinous drop-like corneal dystrophy (GDLD), on the other hand, which was found in Japanese patients in 1914, is a rare autosomal recessive disorder characterized by corneal amyloidosis. Parents of the patients had a markedly higher frequency of consanguineous marriages than the general population. The gene responsible for GDLD, the membrane component, chromosome 1, surface marker 1 (M1S1) gene was mapped to the short arm of chromosome 1(1p). Four deleterious mutations in this gene were detected in Japanese patients. We review here additional studies on mutations of the TGFBI and M1S1 genes found in Japanese patients. In the TGFBI gene, nine different mutations were detected in Japanese patients with GCD, ACD, LCD, or RBCD. The codons R124 and R555 of the TGFBI gene were hotspots in Japanese patients, of whom many were ACD patients with the R124H mutation. New mutations responsible for LCD were detected in the TGFBI gene of patients with LCD, in addition to the P501T mutation in LCD type IIIA found earlier. These studies showed a clear genotype/phenotype correlation associated with the TGFBI gene. In the M1S1 gene, the Q118X mutation was the most common alteration, and a founder mutation in Japanese GDLD patients, as previously reported. Ninety-two percent of the mutated alleles were the Q118X.

[Amiodarone-induced keratopathy].

BACKGROUND: We studied 17 patients who received oral administration of amiodarone. CASES: The patients were 13 males and 4 females with the mean age of 65.7 years. The periods of follow-up observation ranged from 120 to 1,085 days. Keratopathy was found in 7 cases(41.2%), during the follow-up period. The grade of keratopathy showed no fixed tendency in age, total drug dose, or duration of administration, nor was there any correlation between the grade on the one hand and the period from inception of amiodarone administration to the development of keratopathy and total drug dose on the other. The effects of amiodarone on the cornea, conjunctival epithelium, anterior subcapsular lens, and tear fluid were studied histologically in 2 cases. Effects of amiodarone were found in the cornea and anterior subcapsular lens, but not in the conjunctival epithelium and tear fluid. CONCLUSION: It is possible that keratopathy may be an indicator for long-term administration and for predicting the development of other complications of amiodarone.

The expression of laminin-5 and ultrastructure of the interface between basal cells and underlying stroma in the keratoconus cornea.

PURPOSE: We investigated the expression of laminin-5 and integrins, and the ultrastructure of the interface between basal cells and the basement membrane in the keratoconus cornea. These findings were compared to those in normal central cornea and limbus. METHODS: Frozen sections of the normal cornea (center and limbus) and the keratoconus cornea were immunostained with monoclonal antibodies against three chains of laminin-5 and integrins. To investigate the ultrastructure of the interface between basal cells and the underlying stroma, we used transmission electron microscopy. RESULTS: As compared to those in the normal central cornea, immunostaining patterns of the three chains of laminin-5 were thick and irregular in the keratoconus cornea and the normal limbus. Using electron microscopy analysis, the same characteristic structure of the interface between basal cells and the underlying stroma was recognized in the keratoconus cornea and the normal limbus. The expression of integrin alpha(6)beta(4) was restricted to the basal aspect of basal cells in the normal cornea. In the keratoconus cornea, however, integrin alpha(6)beta(4) was expressed in all aspects in basal and suprabasal cells. CONCLUSION The expression patterns of laminin-5 and the ultrastructure of the interface between basal cells and the basement membrane in the keratoconus cornea were similar to those in the normal limbus.

Six different mutations of TGFBI (betaig-h3, keratoepithelin) gene found in Japanese corneal dystrophies.

PURPOSE: To investigate mutations of the human transforming growth factor beta-induced gene (TGFBI), transforming growth factor-beta-induced gene product (betaig-h3, keratoepithelin), in Japanese patients with Avellino corneal dystrophy (ACD), lattice corneal dystrophy (LCD), granular corneal dystrophy (GCD), and Reis-Bücklers corneal dystrophy (RBCD). METHODS: Genomic DNA was extracted from the peripheral blood of 75 patients and 7 unaffected relatives from 60 families with ACD, 34 patients and 8 unaffected relatives from 21 families with LCD, 4 patients and 4 unaffected relatives from 4 families with GCD, and 4 patients and an unaffected relative from 3 families with RBCD. Fifty normal volunteers served as controls. Exons 4, 11, and 12 of the TGFBI gene were amplified by polymerase chain reaction and were directly sequenced. RESULTS: Six different heterozygous missense mutations were detected in codons R124, L518, L527, and R555 of the TGFBI gene in the 117 patients from 88 families. A R124H mutation was detected in the patients with ACD. A R124C mutation was detected in the patients with LCD type 1 (LCD1), L518P was in atypical LCDI, and L527R in LCD with opacities deep in stroma. A R555W mutation was detected in the patients with GCD. A R555Q mutation was detected in the patients with RBCD. CONCLUSIONS: We conclude that codons R124 and R555 of the TGFBI gene are also hot spots in Japanese patients with ACD, LCD, GCD, and RBCD. Many Japanese patients with CD had ACD with R124H mutation. GCD with R555W mutation was rare.

Intraocular Lens Calculation for Cataract Treated with Photorefractive Keratectomy Using Ray Tracing Method.

Purpose: Conventional methods (such as the SRK-II formula) do not accurately calculate the power of the intraocular lens (IOL) after refractive surgery. Therefore, we compared a new formula including a ray tracing method to the conventional method for foldable IOL lens implantation.Method: Foldable IOLs (MA 60 BM) were implanted in 26 patients (32 eyes) using the phakoemulsification technique. The power of the IOL was measured preoperatively using the SRK-II formula in all cases. From the results of postoperative refractive errors of these cases, the power of IOL calculated by the ray tracing method was compared to the SRK-II formula. Cataract patients first treated with photorefractive keratectomy (PRK) received IOL implants using our ray tracing method and their postoperative refraction was measured.Results: The average postoperative refractive error was 1.32 D in SRK-II formula, 0.95 D in the ray tracing method with Ray 1 used and 0.89 D with Ray 2 used. Postoperative refraction of both eyes first treated with PRK was -1.00 D.Conclusion: The average postoperative refractive error was reduced in the ray tracing method using Olsen's predicted ACD (Ray 2) compared to SRK-II formula. This new tracing method appears to be useful for determination of IOL power and it may be applied for IOL calculation for cataract surgery after refractive surgery.

Decreased GlcNAc 6-O-sulfotransferase activity in the cornea with macular corneal dystrophy.

PURPOSE: Macular corneal dystrophy (MCD) is an autosomal recessive inherited disorder that is accompanied by corneal opacity. Explants from MCD-affected corneas have been reported to synthesize low-sulfated KS, suggesting that sulfate groups attached to KS may play critical roles in maintaining corneal transparency. To clear the biosynthetic defect in the MCD cornea, sulfotransferase activities were determined that are presumably involved in the biosynthesis of KS: galactose-6-sulfotransferase (Gal6ST) activity and N-acetylglucosamine 6-O-sulfotransferase (GlcNAc6ST) activity. METHODS: Gal6ST and GlcNAc6ST activities, which were contained in the corneal extracts from corneas affected by MCD and keratoconus and from normal control corneas, were determined by measuring the transfer of (35)SO(4) from [(35)S]3'-phosphoadenosine 5'-phosphosulfate into the Gal residue of partially desulfated KS and the nonreducing terminal GlcNAc residue of GlcNAcbeta1-3Galbeta1-4GlcNAc (oligo A), respectively. RESULTS: The level of Gal6ST activity in corneal extracts from eyes with MCD, which was measured by using partially desulfated KS as an acceptor, was nearly equal to that in eyes with keratoconus and normal control eyes. In contrast, GlcNAc6ST activity in the extracts from MCD-affected corneas, which was measured by using oligo A as an acceptor, was much lower than in those in corneas with keratoconus and in normal control corneas. CONCLUSIONS: The decrease in GlcNAc6ST activity in the cornea with MCD may result in the occurrence of low- or nonsulfated KS and thereby cause corneal opacity.

Q118X mutation of M1S1 gene caused gelatinous drop-like corneal dystrophy: the P501T of BIGH3 gene found in a family with gelatinous drop-like corneal dystrophy.

PURPOSE: To analyze BIGH3 and M1S1 genes in two Japanese brothers with gelatinous drop-like corneal dystrophy and five unaffected family members. METHODS: DNA was extracted, and each part of the two genes was amplified and directly sequenced. RESULTS: On the BIGH3 gene, a heterozygous P501T mutation was found in the elder brother and three unaffected family members. On the M1S1 gene, both brothers with gelatinous drop-like corneal dystrophy showed a homozygous Q118X mutation, whereas all unaffected members were heterozygous. CONCLUSIONS: The Q118X mutation of M1S1 gene caused gelatinous drop-like corneal dystrophy. Although the P501T of the BIGH3 gene found in this pedigree was precisely the one reported for lattice corneal dystrophy IIIA, no clinical feature was shown, even in the 85-year-old father. This fact shows that the P501T mutation for LCDIIIA has low penetrance.

Distribution and isoform characterization of type XII collagen in bovine cornea.

Streptavidin peroxidase immunohistochemistry and immunoelectron microscopy were used to determine the localization of type XII collagen in sections from bovine corneas. Type XII collagen extracted from bovine cornea and skin was assayed by Western blotting. Immunohistochemical experiments showed that type XII collagen was restricted to the corneal stroma; it was not present in corneal epithelium, epithelial basement membrane, Descemet's membrane or endothelium. Type XII collagen was distributed throughout the corneal stroma, and it was prominently localized at the superficial stroma. Immunoelectron-microscopic examination demonstrated that type XII collagen was regularly found along the surface of banded collagen fibrils with a periodic distribution. By Western blot analysis, we observed that extracts from bovine cornea contained both the long and short isoforms of type XII collagen, whereas extracts from bovine skin contained only the short isoform. The homogeneous distribution and/or presence of the long isoform of type XII collagen may be related to the characteristically regular arrangement of collagen fibrils and thereby the transparency of corneal tissue.

Corneal wound healing: Immunohistological features of extracellular matrix following penetrating keratoplasty in rabbits.

PURPOSE: To study the distribution and the constituents of the extracellular matrix in the cornea during wound healing following penetrating keratoplasty (PKP). METHODS: Penetrating keratoplasty (PKP) was performed on albino rabbit eyes, and immunohistochemical techniques were used to determine the distribution of types I, III, IV collagens, large proteoglycans, chondroitin 6-sulfate, chondroitin 4-sulfate, and vimentin. The expression of these substances was determined at postoperative times of 3 days, 1 week, 2 weeks, 1 month, and 3 months. RESULTS: By day 3, staining for type IV collagen was observed along the host-graft junction. By day 7, staining for type III collagen, large proteoglycans, and chondroitin 6-sulfate had increased in the repair region but then decreased with increasing postoperative times. Epithelial wound healing required more than one month, whereas the remodeling of Descemet's membrane did not terminate until 3 months after PKP. CONCLUSION: These results suggest that type III collagen, large proteoglycans, and chondroitin 6-sulfate probably play important roles in corneal wound healing after PKP.

Secondary keratoconus with corneal epithelial iron ring similar to Fleischer's ring.

BACKGROUND: Fleischer's ring is considered to be a characteristic of keratoconus, but we have seen a ring similar to Fleischer's ring in patients with secondary keratoconus, in which the cornea becomes thinner secondarily for undetermined reasons. CASES: We report 6 cases of secondary keratoconus with a corneal epithelial ring similar to the Fleischer's ring pattern. OBSERVATIONS: In these 6 cases (2 men and 4 women), the causes of secondary keratoconus were trachoma in 2 cases, trauma in 2 cases, keratitis in 1 case and unknown etiology in one case. All showed thinning of the cornea and a corneal iron ring similar to Fleischer's ring pattern. The corneal button obtained after keratoplasty in 1 case showed the deposition of hemosiderin in the corneal epithelium after staining with Prussian blue. At the same time we confirmed the existence of iron in the corneal epithelium by x-ray ultimate analysis. CONCLUSIONS: All 6 patients we encountered had a past history of corneal disease in their childhood except for 1 case with unknown etiology. Primary keratoconus is also considered to develop by the early teens at the latest. These facts led us to an assumption that the occurrence of some abnormalities in the cornea during the growth period may result in iron deposition in the epithelium and thinning of the stroma. In light of these facts, abnormalities of the iron metabolism must be thoroughly investigated in considering the etiology of keratoconus.

Trial for new intraocular lens power calculation following phototherapeutic keratectomy.

PURPOSE: To determine an equation to calculate the intraocular lens (IOL) power for eyes that have undergone laser phototherapeutic keratectomy (PTK). METHODS: The Gullstrand series was used to determine the power and radius of curvature of a convex-plane IOL, which will alter the focal point from the cornea to the conjugate point on the retina using the ray tracing method. RESULTS: The radius of curvature of the anterior corneal surface (R), axial length (AXL), the predicted postoperative anterior chamber depth (ACD), and lens thickness (LT) were used in the following formula to calculate the refractive power of the IOL to be used: K = R/7.7, DC = 337.5/R, VC = lOOO/DC x 1.336 where VC is the posterior vertex focal length, A(1) = -(VC - ACD), B(1) = AXL - 0.5 x K - ACD - 0.103LT, S = l/A(1) + l/B(1), K is the proportional expression for anterior corneal curvature, DC = anterior corneal refractive power, A(1) = distance from anterior surface of IOL to posterior vertex focal point, B(1) = distance from the second principal point of IOL to the retina, S = 1/focal length of IOL in air. Using this equation, the power (in diopters) of the IOL in liquid was determined to be 1000/(l/S). 1. 336. In eyes that have undergone PTK, the keratometric value prior to cataract surgery is not used. Instead a value, R', is introduced. R' is defined as (R - 376/1376. dT), where R is the radius of corneal curvature prior to PTK and dT the amount of corneal tissue removed. The corneal thickness after cataract surgery, CT', was defined as CT - dT, where CT is the corneal thickness prior to PTK. CONCLUSION: The new equation appears to be useful for determining the IOL power, although it is important to select a lens that has the accurate predicted anterior chamber depth.

The functions of exogenous and endogenous laminin-5 on corneal epithelial cells.

Recent evidence suggests that the basement membrane not only separates basal cells from Bowman's layer, but also has a crucial role in the proliferation, differentiation and migration of corneal epithelial cells. The basement membrane is composed of a mixture of matrix components including collagens, laminins and heparan sulfate proteoglycans. In these extracellular matrixes, laminin is a major component of the basement membrane. Of 11 laminin isoformes, laminin-5 is a variant, composed of three nonidentical subunits alpha3, beta3, gamma2 and is a major component of the corneal basement membrane. However, little is known about the interactions of laminin-5 with corneal epithelial cells. In this study, we investigated the functions of laminin-5 on SV-40 transfected human corneal epithelial cells (HCE cells). We also revealed different functions between exogenous and endogenous laminin-5 on HCE cells. Laminin-5 is synthesized initially as a 490 kDa molecule that undergoes specific processing to cleavaged isoforms after being secreted. The alpha3 subunit is processed from 200-190 kDa to 160 kDa/145 kDa. The gamma2 subunit is processed from 150 kDa to 105 kDa/80 kDa. The beta3 subunit (140 kDa) is not processed. Exogenously added laminin-5 (soluble form) in this study was purified from a serum-free, conditioned medium of a human gastric carcinoma cell line STKM-I. This soluble laminin is a processed isoform containing alpha3 (160 kDa), beta3 (140 kDa) and gamma2 (105 kDa) chains. On the other hand, immunocytochemical analysis showed that HCE cells themselves secreted laminin-5 endogenously. Western blotting analysis revealed that HCE cells initially produced unprocessed isoform containing 190 kDa alpha3, 140 kDa beta3 and 150 kDa gamma2 chains and that after being secreted, the alpha3 chain was processed to 160 kDa/145 kDa and the gamma2 chain was processed to 105 kDa. Initially we investigated the functions of exogenous (processed) laminin-5 on HCE cells. Exogenously added laminin-5 strongly promoted cell adhesion via alpha3beta1 integrin, cell spreading, assembly of hemidesmosomes and mildly inhibited cell migration. Next we estimated the effect of endogenous (unprocessed) laminin-5 on HCE cells. Using an anti laminin-5 monoclonal antibody (mAb) or anti integrin alpha3beta1 mAbs, the blocking of the interaction between endogenously secreted laminin-5 and HCE cells caused strong inhibition of cell migration. Integrin alpha3beta1 and alpha6beta4 were expressed in HCE cells. These integrins are receptors of laminin-5. But, anti integrin alpha6beta4 mAbs did not have any blocking ability against cell migration. These results indicated that endogenous (unprocessed) laminin-5 has a crucial role in cell migration on HCE cells via alpha3beta1 integrin. In conclusion, structural differences between exogenous (processed) and endogenous (unprocessed) laminin-5 regulated their functions on HCE cells. Exogenously added laminin-5 strongly promoted cell adhesion, cell spreading and assembly of hemidesmosomes. Endogenously secreted laminin-5 had a crucial role in cell migration. In the future, processed soluble laminin-5 could be a useful drug for the prevention of recurrent corneal erosion, and unprocessed soluble laminin-5 could be applied for the treatment of prolonged corneal epithelial defects.

A pathological study on rabbit corneas after laser In situ keratomileusis

Purpose: To investigate pathological changes in rabbit corneas after laser in situ keratomileusis (LASIK).Materials and Methods: We performed LASIK on rabbit corneas to theoretically correct 10.0 diopters of myopia. The corneas were studied pathologically at day 0, and 3 days, 1 week, 3 weeks, 4 months, and 9 months after LASIK. Results: At 3 days after LASIK, keratocytes in the ablated area changed morphologically into fibroblastic cells. And the structure of collagen fibers in the stroma was broken. These changes had disappeared almost entirely at 4 months after LASIK. There were no proliferative changes in the stroma of the ablated cornea 9 months after LASIK. No significant changes were observed in the endothelium. Conclusions: The damage to rabbit corneas induced by LASIK was mild to moderate under the present experimental conditions.

[Intraocular lens calculation for cataract treated with photorefractive keratectomy using ray tracing method].

PURPOSE: Conventional methods (such as the SRK-II formula) do not accurately calculate the power of the intraocular lens (IOL) after refractive surgery. Therefore, we compared a new formula including a ray tracing method to the conventional method for foldable IOL lens implantation. METHOD: Foldable IOLs (MA 60 BM) were implanted in 26 patients (32 eyes) using the phakoemulsification technique. The power of the IOL was measured preoperatively using the SRK-II formula in all cases. From the results of postoperative refractive errors of these cases, the power of IOL calculated by the ray tracing method was compared to the SRK-II formula. Cataract patients first treated with photorefractive keratectomy (PRK) received IOL implants using our ray tracing method and their postoperative refraction was measured. RESULTS: The average postoperative refractive error was 1.32 D in SRK-II formula, 0.95 D in the ray tracing method with Ray 1 used and 0.89 D with Ray 2 used. Postoperative refraction of both eyes first treated with PRK was--1.00 D. CONCLUSION: The average postoperative refractive error was reduced in the ray tracing method using Olsen's predicted ACD (Ray 2) compared to SRK-II formula. This new tracing method appears to be useful for determination of IOL power and it may be applied for IOL calculation for cataract surgery after refractive surgery.

Effect of vitamin A palmitate on vitamin A-deficient rabbits

Purpose: We examined the effects of vitamin A palmitate (VA pal) eyedrops on the symptoms caused by vitamin A-deficiency in rabbits. Methods: Three-week-old rabbits were raised on a vitamin A-deficient diet, and were examined for the quantity of retinol in the serum and the condition of the anterior segment of the eye. The vitamin A-deficient animals were treated with VA pal eyedrops.Results: The retinol in the serum began to decrease 7 months after the animals were placed on the vitamin A-deficient diet. After 10 months, superficial punctate keratitis and the loss of conjunctival goblet cells were observed. Treatment of the disease in the anterior segment of the eyes with VA pal eyedrops resulted in restoration of normal condition within 3 weeks. The treatment increased the goblet cells in the ocular conjunctiva and the retinol in the serum. Conclusions: These results show the efficacy of topical VA pal treatment for vitamin A-deficient rabbits.

[A pathological study on rabbit corneas after laser in situ keratomileusis].

PURPOSE: To investigate pathological changes in rabbit corneas after laser in situ keratomileusis (LASIK). MATERIALS AND METHODS: We performed LASIK on rabbit corneas to theoretically correct 10.0 diopters of myopia. The corneas were studied pathologically at day 0, and 3 days, 1 week, 3 weeks, 4 months, and 9 months after LASIK. RESULTS: At 3 days after LASIK, keratocytes in the ablated area changed morphologically into fibroblastic cells. And the structure of collagen fibers in the stroma was broken. These changes had disappeared almost entirely at 4 months after LASIK. There were no proliferative changes in the stroma of the ablated cornea 9 months after LASIK. No significant changes were observed in the endothelium. CONCLUSIONS: The damage to rabbit corneas induced by LASIK was mild to moderate under the present experimental conditions.