Estimating insulin sensitivity and ß-cell function from the oral glucose tolerance test: validation of a new insulin sensitivity and secretion (ISS) model.

Efficient and accurate methods to estimate insulin sensitivity (SI) and ß-cell function (BCF) are of great importance for studying the pathogenesis and treatment effectiveness of type 2 diabetes (T2D). Existing methods range in sensitivity, input data, and technical requirements. Oral glucose tolerance tests (OGTTs) are preferred because they are simpler and more physiological than intravenous methods. However, current analytical methods for OGTT-derived SI and BCF also range in complexity; the oral minimal models require mathematical expertise for deconvolution and fitting differential equations, and simple algebraic surrogate indices (e.g., Matsuda index, insulinogenic index) may produce unphysiological values. We developed a new insulin secretion and sensitivity (ISS) model for clinical research that provides precise and accurate estimates of SI and BCF from a standard OGTT, focusing on effectiveness, ease of implementation, and pragmatism. This model was developed by fitting a pair of differential equations to glucose and insulin without need of deconvolution or C-peptide data. This model is derived from a published model for longitudinal simulation of T2D progression that represents glucose-insulin homeostasis, including postchallenge suppression of hepatic glucose production and first- and second-phase insulin secretion. The ISS model was evaluated in three diverse cohorts across the lifespan. The new model had a strong correlation with gold-standard estimates from intravenous glucose tolerance tests and insulin clamps. The ISS model has broad applicability among diverse populations because it balances performance, fidelity, and complexity to provide a reliable phenotype of T2D risk.NEW & NOTEWORTHY The pathogenesis of type 2 diabetes (T2D) is determined by a balance between insulin sensitivity (SI) and ß-cell function (BCF), which can be determined by gold standard direct measurements or estimated by fitting differential equation models to oral glucose tolerance tests (OGTTs). We propose and validate a new differential equation model that is simpler to use than current models and requires less data while maintaining good correlation and agreement with gold standards. Matlab and Python code is freely available.

Smg1 haploinsufficiency predisposes to tumor formation and inflammation.

SMG1 is a member of the phosphoinositide kinase-like kinase family of proteins that includes ATM, ATR, and DNA-PK, proteins with known roles in DNA damage and cellular stress responses. SMG1 has a well-characterized role in nonsense-mediated decay as well as suggested roles in the DNA damage response, resistance to oxidative stress, regulation of hypoxic responses, and apoptosis. To understand the roles of SMG1 further, we generated a Genetrap Smg1 mouse model. Smg1 homozygous KO mice were early embryonic lethal, but Smg1 heterozygous mice showed a predisposition to a range of cancers, particularly lung and hematopoietic malignancies, as well as development of chronic inflammation. These mice did not display deficiencies in known roles of SMG1, including nonsense-mediated decay. However, they showed elevated basal tissue and serum cytokine levels, indicating low-level inflammation before the development of tumors. Smg1 heterozygous mice also showed evidence of oxidative damage in tissues. These data suggest that the inflammation observed in Smg1 haploinsufficiency contributes to susceptibility to cancer and that Smg1-deficient animals represent a model of inflammation-enhanced cancer development.

Estimating Insulin Sensitivity and Beta-Cell Function from the Oral Glucose Tolerance Test: Validation of a new Insulin Sensitivity and Secretion (ISS) Model.

Efficient and accurate methods to estimate insulin sensitivity (SI) and beta-cell function (BCF) are of great importance for studying the pathogenesis and treatment effectiveness of type 2 diabetes. Many methods exist, ranging in input data and technical requirements. Oral glucose tolerance tests (OGTTs) are preferred because they are simpler and more physiological. However, current analytical methods for OGTT-derived SI and BCF also range in complexity; the oral minimal models require mathematical expertise for deconvolution and fitting differential equations, and simple algebraic models (e.g., Matsuda index, insulinogenic index) may produce unphysiological values. We developed a new ISS (Insulin Secretion and Sensitivity) model for clinical research that provides precise and accurate estimates of SI and BCF from a standard OGTT, focusing on effectiveness, ease of implementation, and pragmatism. The model was developed by fitting a pair of differential equations to glucose and insulin without need of deconvolution or C-peptide data. The model is derived from a published model for longitudinal simulation of T2D progression that represents glucose-insulin homeostasis, including post-challenge suppression of hepatic glucose production and first- and second-phase insulin secretion. The ISS model was evaluated in three diverse cohorts including individuals at high risk of prediabetes (adult women with a wide range of BMI and adolescents with obesity). The new model had strong correlation with gold-standard estimates from intravenous glucose tolerance tests and hyperinsulinemic-euglycemic clamp. The ISS model has broad clinical applicability among diverse populations because it balances performance, fidelity, and complexity to provide a reliable phenotype of T2D risk.

Corneal Backscatters as an Objective Index for Assessing Fuchs' Endothelial Corneal Dystrophy: A Pilot Study.

PURPOSE: To provide an objective, quantitative approach for monitoring Fuchs' endothelial corneal dystrophy (FECD), with Scheimpflug imaging. DESIGN: This is a retrospective case-control pilot study. METHODS: The study group consisted of 53 eyes in 27 patients diagnosed with FECD, with normal subjects paired as control. Main outcome measures were corneal thickness, morphological patterns on densitograms, and indices of corneal density including the average area density (mean AD) and the average ratio of Descemet's membrane density versus area density (DM/AD) in Pentacam Scheimpflug images. RESULTS: There were no significant differences in age and corneal thickness between FECD and normal groups. Morphologically, hanging-hammock patterns were noted on the densitograms of FECD patients, which were different from the high-back chair patterns in normal subjects. Quantitatively, mean AD and DM/AD were both elevated in FECD patients as compared with normal subjects (P = 0.01 and 0.025, resp.). In addition, FECD patients with corneal edema had significantly higher mean AD (P = 0.018) than those without corneal edema. CONCLUSIONS: This pilot study shows that Pentacam system provides an objective, quantitative way to approach FECD corneas. It can assist ophthalmologists in detecting the early change and in monitoring disease progression of FECD. Further studies are needed to consolidate the findings.

Shifting trends in microbial keratitis following penetrating keratoplasty in Taiwan.

To investigate the clinical and microbiological profiles from microbial keratitis following penetrating keratoplasty (PKP) in a tertiary referral center in Taiwan, the medical records of 648 consecutive patients (648 eyes) undergoing PKP between January 2003 and December 2007 were retrospectively reviewed. Patients who subsequently sustained microbial keratitis were enrolled and analyzed for potential risk factors, clinical manifestations, microbiological profiles, complications, graft survival, and final visual outcome. A total number of 42 corneal graft infections (6.5%) were recruited. Mean interval between corneal transplantation and graft infection was 12 ±â€Š9.5 months. Potential risk factors included suture-related problems (31.0%), lid abnormalities (23.8%), persistent epithelial defect (23.8%), contact lens use (14.3%), dry eye (11.9%), and prior rejection episodes (4.8%). Lesions were discovered mostly at the donor-recipient junction ([DRJ] 45.2%). Positive cultures were identified in all of the morbid eyes, of which Pseudomonas aeruginosa was the most common pathogen (38.1%). Despite mandatory hospitalization and topical fortified antibiotics management, complications ensued such as graft failure (71.4%), hypopyon (21.4%), corneal perforation (14.3%), wound dehiscence (11.9%), and endophthalmitis (4.8%). The visual outcome was dismal that graft clarity was achieved in only 12 eyes (28.6%), and that final visual acuity deteriorated to less than 20/200 in 28 eyes (66.7%). In conclusion, microbial keratitis following PKP is a devastating event that severely impairs graft survival rate and postoperative visual outcome which usually occur within the first postoperative year. The incidence of post-PKP microbial keratitis has generally decreased in recent years whilst P. aeroginosa prevails as the leading cause of graft infection in our hospital. Close follow-up by ophthalmologists and elevated self-awareness of patients for at least one year are always encouraged to prevent late-onset infection.

Shifting Trends in Bacterial Keratitis in Taiwan: A 10-Year Review in a Tertiary-Care Hospital.

PURPOSE: To investigate the distribution, current trends, and antibiotic susceptibility profiles of bacterial keratitis isolates over 10 years. METHODS: We retrospectively reviewed the microbiology records of all corneal scrapings undertaken for cultures at Chang Gung Memorial Hospital from 2003 through 2012. We identified bacterial isolates and verified antibiotic susceptibilities by using the disk diffusion method. The Mantel-Haenszel linear-by-linear association χ test was used to detect the trends. RESULTS: We collected 2012 corneal scrapings, and the culture was positive in 992 samples (49.3%), yielding 1282 isolates. Bacterial isolates were identified for 1039 isolates (81.1%), including 533 gram-positive and 506 gram-negative isolates. An increase in the percentage of gram-positive isolates was significant (P = 0.008), as was a decrease in that of gram-negative isolates (P = 0.002). The most common bacterial isolates were Pseudomonas aeruginosa (24.4%) and coagulase-negative Staphylococcus (16.6%). For gram-positive organisms, the susceptibilities were as follows: vancomycin 100%, ciprofloxacin 88.9%, sulfamethoxazole-trimethoprim 86.8%, clindamycin 73.2%, and oxacillin 56.5%. The susceptibility of gram-positive bacteria to clindamycin and oxacillin increased significantly (P = 0.009 and P = 0.001). For gram-negative organisms, the susceptibilities were as follows: ciprofloxacin 93.7%, piperacillin 91.9%, ceftazidime 90.9%, amikacin 88.3%, and gentamicin 84.7%. No change in trend occurred. CONCLUSIONS: In Taiwan, we documented an increasing trend in the percentage of gram-positive bacteria. Methicillin-resistant microorganisms accounted for 43.5% of all gram-positive bacteria, but the trend of resistance to oxacillin and clindamycin significantly decreased. Ciprofloxacin continued to be a good empiric antibiotic for treating bacterial keratitis.

Clinical Characteristics of Stenotrophomonas maltophilia Keratitis.

PURPOSE: Stenotrophomonas maltophilia is an important opportunistic pathogen but an uncommon cause of corneal infections. This study aimed to report the clinical features, antibiotic susceptibility, treatments, and visual outcomes of S. maltophilia keratitis. METHODS: The medical records of 21 patients with culture-proven S. maltophilia-associated infectious keratitis in our hospital between January 1, 2003, and December 31, 2014, were retrospectively reviewed. The clinical features of patients with S. maltophilia keratitis were compared with those of patients from 17 previously reported cases. RESULTS: The most common risk factors for S. maltophilia keratitis were preexisting corneal disease or previous corneal surgery (16), followed by soft contact lens wear (9). Nine patients (42.9%) were multifactorial. Polymicrobial infections was detected in 12 eyes (57.1%). All S. maltophilia isolates were susceptible to levofloxacin and moxifloxacin. A total of 17 of 21 patients (81.0%) had favorable responses to topical antimicrobial treatment, and 10 (47.6%) required surgical intervention for promotion of reepithelialization (6) and corneal perforation (4). Final vision ranged from light perception to 20/20. The clinical features of S. maltophilia keratitis in our cases and in previously reported cases were similar. CONCLUSIONS: S. maltophilia keratitis primarily affects patients with compromised ocular surfaces. S. maltophilia demonstrates in vitro susceptibility and a strong clinical response to fluoroquinolones.

Role of matrix metalloproteinase-9 in ex vivo expansion of human limbal epithelial cells cultured on human amniotic membrane.

PURPOSE: To investigate the expression and pivotal role of matrix metalloproteinase (MMP)-9 in the ex vivo expansion of human limbal explants with or without amniotic membrane (AM). METHODS: Corneoscleral buttons were cultured on intact, denuded AM or plastic dishes for 3 weeks. To determine the role of MMP-9 in cell migration, either the MMP inhibitor GM6001 or an MMP-9 antibody was used. Expression of MMP-9 was determined by gelatin zymography, reverse transcription-polymerase chain reaction, and immunohistochemical staining. RESULTS: The expression of MMP-9 in all culture conditions increased in a time-dependent manner. However, the active form of MMP-9 emerged only in cultures on both intact and denuded AM from the second week. The averaged corrected ratio of MMP-9 expression in cultures on intact AM versus those on denuded AM or plastic dishes was 2.76 +/- 0.69- or 4.25 +/- 0.30-fold, respectively, when total RNA was used as an internal control. MMP-9 transcripts were upregulated in cultures on intact AM compared with the other two culture conditions. Immunohistochemical staining demonstrated that the MMP-9 protein was located on the limbal epithelial cells. Upregulation of MMP-9 associated with cell migration was significantly attenuated by both GM6001 and MMP-9 antibody, consistent with the inhibition of MMP-9 activity, as determined by gelatin zymography. In contrast, the sizes of limbal outgrowth were not different between the control and MMP-9 antibody-treated plastic dishes. CONCLUSIONS: These results demonstrated that MMP-9 not only was upregulated, it was also involved in the outgrowth of limbal epithelial cells. These results suggest that cell-cell matrix interaction is involved in the expansion of limbal epithelial cells on intact AM, and MMP-9 may be a key element.

Risk Factors and Microbiological Features of Patients Hospitalized for Microbial Keratitis: A 10-Year Study in a Referral Center in Taiwan.

We conducted a retrospective, cross-sectional study to analyze predisposing factors, clinical features, and microbiological characteristics of patients with microbial keratitis hospitalized over 10 years.The medical records of 558 patients who were diagnosed with microbial keratitis and admitted to Chang Gung Memorial Hospital (CGMH), a referral center in Taiwan, from January 1, 2003 to December 31, 2012 were reviewed. Demographics, predisposing factors, isolated organisms, treatment, and hospital stay were recorded. Yearly trends were tested using a linear-by-linear association.Contact lens wear was the most common predisposing factor (31.4%), followed by ocular and systemic diseases (26.3%) and trauma (23.5%). Contact lens-related infectious keratitis increased year by year (P = 0.011). Pseudomonas aeruginosa was the most commonly isolated organism (28%), followed by fungi (17.6%) and coagulase-negative Staphylococcus (5.4%). Except for Serratia marcescens, the identified organisms did not change over 10 years. Most bacterial infections were controlled using antimicrobial treatment, but more than half of patients with fungal keratitis required surgical interventions. The mean hospital stay was 13.7 ±â€Š11.5 days. Previous ocular surgery, large ulcer size, nontuberculous myycobacteris infection, and surgery during admission were related to prolonged hospital stay.In Taiwan, contact lens-related pseudomonal keratitis remained the most common cause of microbial keratitis in patients hospitalized from 2003 to 2012.

Methicillin-Resistant Staphylococcus aureus Ocular Infection in Taiwan: Clinical Features, Genotying, and Antibiotic Susceptibility.

Methicillin-resistant Staphylococcus aureus (MRSA) infection is an important public health issue. This observational study aimed to characterize clinical features, antibiotic susceptibility, and genotypes of ocular infections caused by MRSA based on the clinical and molecular definitions of community-associated (CA) and healthcare-associated (HA) strains.Fifty-nine patients with culture-proven S aureus ocular infection were enrolled from January 1, 2010 to December 31, 2011 at Chang Gung Memorial Hospital, Taiwan. Antibiotic susceptibility was verified using disk diffusion/E test. For characterization, staphylococcal cassette chromosome mec (SCCmec), pulsed-field gel electrophoresis (PFGE), multilocus sequence type (MLST), and Panton-Valentine leukocidin (PVL) gene, were performed. MRSA isolates from the patients with HA factors were classified as clinically defined HA-MRSA, and those carrying SCCmec type I to III as molecularly defined HA-MRSA.Thirty-four patients with MRSA ocular infection were identified. The most common clone of CA-MRSA and HA-MRSA isolates was ST59/PFGE type D/SCCmec IV,VT/PVL (+) (n = 12) and CC 239/PFGE type A/SCCmec III, IIIA/PVL(-) (n = 10), respectively. All the 11 patients with molecularly defined HA-MRSA infections and 50% of the 22 patients with molecularly defined CA-MRSA infections were found to have HA factors (P = .005). CA-MRSA tended to cause lid infections, whereas HA-MRSA tended to cause corneal infections. Contrary to HA-MRSA isolates, nearly all the CA-MRSA isolates were susceptible to trimethoprim/sulfamethoxazole and fluoroquinolones under either clinical or molecular classifications.In Taiwan, CA-MRSA isolates exhibited considerably higher susceptibility to fluoroquinolones when compared with HA-MRSA isolates. A strong correlation was observed between the HA factors and molecularly defined HA-MRSA isolates.

Retained Descemet's membrane after penetrating keratoplasty.

Retained Descemet's membrane is a rare complication of penetrating keratoplasty (PKP). The membrane can become progressively opaque and threaten the health of the corneal graft. We report such a case involving a 53-year-old man. Simultaneous surgical removal of the membrane and phacoemulsification with intraocular lens implantation were performed 3 months after PKP. The graft remained clear and best corrected visual acuity was 20/20 2 years after secondary surgery.

Combination of adult inclusion conjunctivitis and mucosa-associated lymphoid tissue (MALT) lymphoma in a young adult.

PURPOSE: To report a patient who was diagnosed with combined adult inclusion conjunctivitis (AIC) and mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: This is a case report. RESULTS: An 18-year-old male patient presented with chronic conjunctivitis and giant follicles. Evaluation by chlamydial antigen assay was positive. Conjunctival biopsy for the immunohistochemical stain and polymerase chain reaction of the left eye showed MALT lymphoma. CONCLUSIONS: MALT lymphoma can masquerade as other ocular surface diseases. Chlamydial infection causes chronic inflammation of the conjunctiva. Both of these diseases should be considered as a differential diagnosis of refractory follicular conjunctivitis. It is worthy of further study to determine whether chronic inflammation resulting from chlamydial infection increases the risk of MALT lymphoma or it is coincidental.

The progressive changes of nasal symmetry and growth after nasoalveolar molding: a three-year follow-up study.

The purpose of this study was to assess the progressive changes of nasal symmetry, growth, and relapse after presurgical nasoalveolar molding and primary cheiloplasty in unilateral complete cleft lip/palate infants. Twenty-five consecutive complete unilateral cleft lip/palate infants were included. All the infants underwent nasoalveolar molding before primary cheiloplasty. Standard 1:1 ratio basilar photographs were taken before and after nasoalveolar molding, 1 week after cheiloplasty, and yearly for 3 years. Linear measurements were made directly on the photographs. The results of this study revealed that the nasal asymmetry was significantly improved after nasoalveolar molding and was further corrected to symmetry after primary cheiloplasty. After the primary cheiloplasty, the nasal asymmetry significantly relapsed in the first year postoperatively and then remained stable and well afterward. The relapse was the result of a significant differential growth between the cleft and noncleft sides in the first year postoperatively. To compensate for relapse and differential growth, the authors recommend (1) narrowing down the alveolar cleft as well as possible by nasoalveolar molding, (2) overcorrecting the nasal vertical dimension surgically, and (3) maintaining the surgical results using a nasal conformer.

Clinical characteristics of alternaria keratitis.

Purpose. Alternaria spp. are an uncommon cause of mycotic keratitis. Previous studies on Alternaria keratitis have generally been limited to case reports. We examined the clinical characteristics of Alternaria keratitis in this study. Methods. The characteristics and outcomes of 7 patients with culture-proven Alternaria keratitis treated in our hospital were compared with 25 previously reported cases. Results. The risk factors for Alternaria keratitis were trauma in 5 patients and soft contact lenses in 1 patient. Six patients with early diagnosis (<2 weeks) were cured with medical antimicrobial treatment; a patch graft was required in 1 patient with perforation. When incorporated with previous reports on Alternaria keratitis (n = 32), 14 (44%) infections followed trauma, 10 (31%) were associated with preexisting corneal disease or previous ocular surgery, and 5 (16%) occurred in soft contact lens wearers. Successful medical treatment was achieved in 23 (72%) patients, including 10 out of 21 eyes (48%) treated with natamycin and/or amphotericin B. Therapeutic penetrating keratoplasty was performed in 9 (28%) cases. Conclusions. Alternaria keratitis is generally associated with specific risk factors and responds to medical treatment when early diagnosis is performed and prompt antifungal treatment is initiated.

Pediatric microbial keratitis in Taiwan: clinical and microbiological profiles, 1998-2002 versus 2008-2012.

PURPOSE: To identify the change in clinical and microbiological profiles of pediatric microbial keratitis in Taiwan between 1998-2002 and 2008-2012. DESIGN: Retrospective, observational study. METHOD: setting: Chang Gung Memorial Hospital, a referral center in Taiwan. patient population: We retrospectively reviewed the medical records of 68 eyes of 67 children aged 16 years or younger who were diagnosed with microbial keratitis and treated at our hospital between July 2008 and December 2012. main outcomes and measures: Predisposing factors, isolated organisms, antibiotic susceptibility, and clinical outcomes. The findings were compared with the results of our previous study conducted between July 1998 and December 2002. RESULTS: As in 1998-2002, the leading risk factor for microbial keratitis during 2008-2012 was contact lens use, and the infection rate significantly increased from 40.7% to 52.9% (P = .024), which was mainly attributable to the recent increase in the rate of orthokeratology-related keratitis from 9.9% to 19.1% (P = .011). Pseudomonas aeruginosa remained the most commonly isolated organism (30.6%), but the number of isolated coagulase-negative Staphylococcus cases increased significantly in the 2008-2012 cases (P = .04). Antibiotic susceptibility of organisms did not change significantly between the 2 study periods. By using multiple linear stepwise regression analysis, we found that gram-negative bacterial infection played a crucial role in poor visual outcome. CONCLUSIONS: Contact lens-related microbial keratitis increased in Taiwanese children over time, especially because of the use of overnight orthokeratology. Clinicians must understand the infection background and pay further attention to contact lens use in pediatric patients.

Staphylococcus aureus keratitis: a review of hospital cases.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection is an important public health issue. The study aimed to characterize the patient demographics, clinical features, antibiotic susceptibility, and clinical outcomes of keratitis caused by S. aureus, and to make a comparison between MRSA and methicillin-sensitive S. aureus (MSSA) isolates. METHODOLOGY/PRINCIPAL FINDINGS: Patients (n = 59) with culture-proven S. aureus keratitis treated in Chang Gung Memorial Hospital between January 1, 2006, and December 31, 2010, were included in our study. Patients' demographic and clinical data were retrospectively reviewed. Twenty-six MRSA (44%) and 33 MSSA (56%) isolates were collected. The MRSA keratitis was significantly more common among the patients with healthcare exposure (P = 0.038), but 46.2% (12/26) of patients with MRSA keratitis were considered to have community-associated infections. All isolates were susceptible to vancomycin. MRSA isolates were significantly more resistant to clindamycin, erythromycin, and sulfamethoxazole/trimethoprim. Ocular surface disease was a significant risk factor for MRSA keratitis (P = 0.011). Visual outcome did not differ significantly between the MRSA and MSSA groups. However, age (B = 0.01, P = 0.035, 95% confidence interval [CI]: 0.001-0.019) and visual acuity at presentation (B = 0.749, P<0.001, 95% CI: 0.573-0.926) were significantly correlated with visual outcome. CONCLUSIONS/SIGNIFICANCE: Ocular surface disease is an important predisposing factor for S. aureus keratitis, especially for MRSA infections. Advanced age and poor visual acuity at presentation are important prognostic indicators for poor visual outcome in S. aureus keratitis. Oxacillin resistance may not be a significant prognostic indicator.

Therapeutic penetrating keratoplasty in severe infective keratitis using glycerol-preserved donor corneas.

PURPOSE: To report the surgical outcome of therapeutic penetrating keratoplasty (TPKP) using glycerol-preserved donor corneas in severe infective keratitis. METHODS: Glycerol-preserved corneas were obtained from the recipient corneas of the patients who underwent optical penetrating keratoplasty and preserved in glycerol. Eight eyes of 8 patients (3 men/5 women; average age, 69.7 years) with severe corneal ulcer with perforation were treated with TPKP using glycerol-preserved corneas. RESULTS: With a mean follow-up time of 31.1 months (range, 9-58 months), satisfactory anatomical integrity was obtained in 7 patients (87.5%) at the end of the follow-up. Eradication of infection without recurrence was obtained in 7 eyes (87.5%). The mean reepithelialization time was 10.2 days. One patient (12.5%) received secondary optical penetrating keratoplasty. The pre-TPKP visual acuity ranged from no light perception to 0.06. After surgery, 4 eyes (50%) improved or maintained preoperative visual acuity and four eyes (50%) had no light perception but maintained anatomical integrity. One had a recurrent infection and needed antibiotics and amniotic membrane graft. One suffered from secondary glaucoma and received evisceration 19 months later. CONCLUSIONS: Glycerol-preserved donor corneas may be effective substitutes in TPKP to control severe infective keratitis and preserve anatomical integrity.

Primary phacoemulsification and intraocular lens implantation for acute primary angle-closure.

BACKGROUND: To investigate the effect of primary phacoemulsification on intraocular pressure (IOP) in patients with acute primary angle-closure (PAC) and coexisting cataract. METHODOLOGY: Sixteen eyes of 14 patients with acute PAC received phacoemulsification and intraocular lens implantation as initial management for medically uncontrolled IOP in a retrospective chart review. The effects on IOP, vision, anterior chamber depth (ACD), and number of antiglaucoma medications were evaluated. PRINCIPAL FINDINGS: The postoperative IOP was reduced in 16 eyes (100%). The mean ± standard deviation preoperative IOP was 48.81 ± 16.83 mm Hg, which decreased postoperatively to 16.46 ± 10.67 mm Hg at 1 day, 9.43 ± 3.03 mm Hg at 1 week, 9.49 ± 2.14 mm Hg at 2 weeks, 10.78 ± 3.56 mm Hg at 1 month, and 10.70 ± 2.80 mm Hg at 3 months (p < 0.001). The mean number of antiglaucoma medications decreased from 3.56 ± 1.14 to 0.13 ± 0.34 (p < 0.001). The average preoperative ACD was 2.08 ± 0.35 mm, which increased to 3.59 ± 0.33 mm after surgery (p < 0.001). Visual acuity (converted into logarithm of the minimum angle of resolution [logMAR]) improved from 1.14 ± 0.71 to 0.73 ± 0.53 (p =  0.001). CONCLUSIONS: Primary phacoemulsification plus intraocular lens implantation lowered IOP, reduced the use of antiglaucoma medications, and improved vision in patients with acute PAC. This is a safe and effective method of IOP control and can be considered a first treatment option in managing patients with acute PAC and coexisting cataract.

Expression of a truncated Brca1 protein delays lactational mammary development in transgenic mice.

To address the hypothesis that certain disease-associated mutants of the breast-ovarian cancer susceptibility gene BRCA1 have biological activity in vivo, we have expressed a truncated Brca1 protein (trBrca1) in cell-lines and in the mammary gland of transgenic mice. Immunofluorescent analysis of transfected cell-lines indicates that trBRCA1 is a stable protein and that it is localized in the cell cytoplasm. Functional analysis of these cell-lines indicates that expression of trBRCA1 confers an increased radiosensitivity phenotype on mammary epithelial cells, consistent with abrogation of the BRCA1 pathway. MMTV-trBrca1 transgenic mice from two independent lines displayed a delay in lactational mammary gland development, as demonstrated by altered histological profiles of lobuloalveolar structures. Cellular and molecular analyses indicate that this phenotype results from a defect in differentiation, rather than altered rates of proliferation or apoptosis. The results presented in this paper are consistent with trBrca1 possessing dominant-negative activity and playing an important role in regulating normal mammary development. They may also have implications for germline carriers of BRCA1 mutations.