A novel treatment strategy utilizing panobinostat for high-risk and treatment-refractory hepatoblastoma.

BACKGROUND & AIMS: Patients with metastatic, treatment-refractory, and relapsed hepatoblastoma (HB) have survival rates of less than 50% due to limited treatment options. To develop new therapeutic strategies for these patients, our laboratory has developed a preclinical testing pipeline. Given that histone deacetylase (HDAC) inhibition has been proposed for HB, we hypothesized that we could find an effective combination treatment strategy utilizing HDAC inhibition. METHODS: RNA sequencing, microarray, NanoString, and immunohistochemistry data of patient HB samples were analyzed for HDAC class expression. Patient-derived spheroids (PDSp) were used to screen combination chemotherapy with an HDAC inhibitor, panobinostat. Patient-derived xenograft (PDX) mouse models were developed and treated with the combination therapy that showed the highest efficacy in the PDSp drug screen. RESULTS: HDAC RNA and protein expression were elevated in HB tumors compared to normal livers. Panobinostat (IC50 of 0.013-0.059 µM) showed strong in vitro effects and was associated with lower cell viability than other HDAC inhibitors. PDSp demonstrated the highest level of cell death with combination treatment of vincristine/irinotecan/panobinostat (VIP). All four models responded to VIP therapy with a decrease in tumor size compared to placebo. After 6 weeks of treatment, two models demonstrated necrotic cell death, with lower Ki67 expression, decreased serum alpha fetoprotein and reduced tumor burden compared to paired VI- and placebo-treated groups. CONCLUSIONS: Utilizing a preclinical HB pipeline, we demonstrate that panobinostat in combination with VI chemotherapy can induce an effective tumor response in models developed from patients with high-risk, relapsed, and treatment-refractory HB. IMPACT AND IMPLICATIONS: Patients with treatment-refractory hepatoblastoma have limited treatment options with survival rates of less than 50%. Our manuscript demonstrates that combination therapy with vincristine, irinotecan, and panobinostat reduces the size of high-risk, relapsed, and treatment-refractory tumors. With this work we provide preclinical evidence to support utilizing this combination therapy as an arm in future clinical trials.

Identifying biomarkers of differential chemotherapy response in TNBC patient-derived xenografts with a CTD/WGCNA approach.

Although systemic chemotherapy remains the standard of care for TNBC, even combination chemotherapy is often ineffective. The identification of biomarkers for differential chemotherapy response would allow for the selection of responsive patients, thus maximizing efficacy and minimizing toxicities. Here, we leverage TNBC PDXs to identify biomarkers of response. To demonstrate their ability to function as a preclinical cohort, PDXs were characterized using DNA sequencing, transcriptomics, and proteomics to show consistency with clinical samples. We then developed a network-based approach (CTD/WGCNA) to identify biomarkers of response to carboplatin (MSI1, TMSB15A, ARHGDIB, GGT1, SV2A, SEC14L2, SERPINI1, ADAMTS20, DGKQ) and docetaxel (c, MAGED4, CERS1, ST8SIA2, KIF24, PARPBP). CTD/WGCNA multigene biomarkers are predictive in PDX datasets (RNAseq and Affymetrix) for both taxane- (docetaxel or paclitaxel) and platinum-based (carboplatin or cisplatin) response, thereby demonstrating cross-expression platform and cross-drug class robustness. These biomarkers were also predictive in clinical datasets, thus demonstrating translational potential.

Bleb revision with bleborhexis and clear corneal lamellar patch graft for overhanging cystic bleb.

Background: Trabeculectomy is associated with several complications. One of the common complications with mitomycin assisted trabeculectomy is thin cystic bleb leading to bleb leak, hypotony and infections. Various technique of bleb repair and reconstruction have been described, such as conjunctival advancement, or scleral, pericardial or corneal patch graft. Purpose: To demonstrate bleb revision by bleborhexis and clear corneal lamellar patch graft for a patient with thin cystic leaking bleb leading to hypotony and decreased vision. Synopsis: This was a 75-year-old one-eyed lady, diagnosed with primary angle-closure glaucoma in both eyes with absent light perception in the left eye, had undergone a combined trabeculectomy and cataract surgery in the right eye 6 years ago. She presented with diminution of vision (6/18p), introacular pressure (IOP) of of 6 mmHg, thin cystic leaking overhanging bleb, and dysesthesia. Bleb repair by bleborhexis with lamellar corneal patch graft was performed. Bleborhexis is a technique in which the overhanging fibrosed thin cystic conjunctival bleb is peeled off the cornea smoothly to leave a uniform clear corneal surface. Clear cornea, uniform diffuse bleb, well-formed anterior chamber with and IOP of 15 mmHg was noted on the first post-operative day, with a vision of 6/12p. This procedure helped meticulous reconstruction of the bleb, early recovery of vision, maintanance of normotensive eye, and save the eye from potential infections. Highlights: Bleborhexis with lamellar corneal patch graft provides for an easy and a elegant surgical technique with minimal corneal tissue damage, faster healing and patient comfort. It could be the favored technique in patients with thin overhanging clebs. Video link: https://youtu.be/GeFYHWToueU.

Factors associated with mortality in patients with COVID-19 admitted to intensive care: a systematic review and meta-analysis.

Identification of high-risk patients admitted to intensive care with COVID-19 may inform management strategies. The objective of this meta-analysis was to determine factors associated with mortality among adults with COVID-19 admitted to intensive care by searching databases for studies published between 1 January 2020 and 6 December 2020. Observational studies of COVID-19 adults admitted to critical care were included. Studies of mixed cohorts and intensive care cohorts restricted to a specific patient sub-group were excluded. Dichotomous variables were reported with pooled OR and 95%CI, and continuous variables with pooled standardised mean difference (SMD) and 95%CI. Fifty-eight studies (44,305 patients) were included in the review. Increasing age (SMD 0.65, 95%CI 0.53-0.77); smoking (OR 1.40, 95%CI 1.03-1.90); hypertension (OR 1.54, 95%CI 1.29-1.85); diabetes (OR 1.41, 95%CI 1.22-1.63); cardiovascular disease (OR 1.91, 95%CI 1.52-2.38); respiratory disease (OR 1.75, 95%CI 1.33-2.31); renal disease (OR 2.39, 95%CI 1.68-3.40); and malignancy (OR 1.81, 95%CI 1.30-2.52) were associated with mortality. A higher sequential organ failure assessment score (SMD 0.86, 95%CI 0.63-1.10) and acute physiology and chronic health evaluation-2 score (SMD 0.89, 95%CI 0.65-1.13); a lower PaO2 :FI O2 (SMD -0.44, 95%CI -0.62 to -0.26) and the need for mechanical ventilation at admission (OR 2.53, 95%CI 1.90-3.37) were associated with mortality. Higher white cell counts (SMD 0.37, 95%CI 0.22-0.51); neutrophils (SMD 0.42, 95%CI 0.19-0.64); D-dimers (SMD 0.56, 95%CI 0.43-0.69); ferritin (SMD 0.32, 95%CI 0.19-0.45); lower platelet (SMD -0.22, 95%CI -0.35 to -0.10); and lymphocyte counts (SMD -0.37, 95%CI -0.54 to -0.19) were all associated with mortality. In conclusion, increasing age, pre-existing comorbidities, severity of illness based on validated scoring systems, and the host response to the disease were associated with mortality; while male sex and increasing BMI were not. These factors have prognostic relevance for patients admitted to intensive care with COVID-19.

Interleukin 4 induces apoptosis of acute myeloid leukemia cells in a Stat6-dependent manner.

Cytokines provide signals that regulate immature normal and acute myeloid leukemia (AML) cells in the bone marrow microenvironment. We here identify interleukin 4 (IL4) as a selective inhibitor of AML cell growth and survival in a cytokine screen using fluorescently labeled AML cells. RNA-sequencing of the AML cells revealed an IL4-induced upregulation of Stat6 target genes and enrichment of apoptosis-related gene expression signatures. Consistent with these findings, we found that IL4 stimulation of AML cells induced Stat6 phosphorylation and that disruption of Stat6 using CRISPR/Cas9-genetic engineering rendered cells partially resistant to IL4-induced apoptosis. To evaluate whether IL4 inhibits AML cells in vivo, we expressed IL4 ectopically in AML cells transplanted into mice and also injected IL4 into leukemic mice; both strategies resulted in the suppression of the leukemia cell burden and increased survival. Notably, IL4 exposure caused reduced growth and survival of primary AML CD34+CD38- patient cells from several genetic subtypes of AML, whereas normal stem and progenitor cells were less affected. The IL4-induced apoptosis of AML cells was linked to Caspase-3 activation. Our results demonstrate that IL4 selectively induces apoptosis of AML cells in a Stat6-dependent manner-findings that may translate into new therapeutic opportunities in AML.

Open angle glaucoma in a case of Type IV Ehler Danlos syndrome: a rarely reported association.

A 26-year-old male presented to us with defective vision in the left eye. He had best corrected visual acuity (BCVA) of hand movement (HM) in right eye and 6/9 in left eye. He had ptosis with ectropion in both eyes and relative afferent pupillary defect (RAPD) in right eye. Intraocular pressure (IOP) was 46 and 44 mmHg in right and left eye, respectively. Fundus showed glaucomatous optic atrophy (GOA) in right eye and cup disc ratio (CDR) of 0.75 with bipolar rim thinning in left eye. Systemic examination showed hyperextensible skin and joints, acrogeria, hypodontia, high arched palate, and varicose veins. He gave history of easy bruising and tendency to fall and history of intestinal rupture 5 years ago for which he had undergone surgery. He was diagnosed as a case of Type IV Ehler-Danlos syndrome (EDS) with open angle glaucoma. He underwent trabeculectomy in both eyes. This is a rare case that shows glaucoma in a patient of EDS Type IV. Very few such cases have been reported in literature.

A study of initial therapy for glaucoma in southern India: India Glaucoma Outcomes and Treatment (INGOT) Study.

PURPOSE: To compare initial glaucoma therapy with medications and trabeculectomy in southern India. METHODS: Patients aged ≥ 30 years newly diagnosed with glaucoma were randomized to trabeculectomy with 5-fluorouracil or medical therapy. Subjects with best-corrected vision <6/18 due to cataract underwent phacoemulsification (phaco/intraocular lens, IOL). Intraocular pressure (IOP), vision and visual function were assessed at 12 months. RESULTS: Patients assigned to medications and surgery received the expected therapy in 86% (172/199) and 64% (126/199) of cases, respectively. Forty patients (20%) assigned to surgery refused any treatment and 33 (17%) received medications. Among 199 patients randomized to medications, 52 (26.1%) underwent phaco/IOL, as did 89/199 (43.7%) of patients randomized to trabeculectomy. Baseline parameters of the two groups did not differ, nor did 1-year follow-up rates (medication 65%, trabeculectomy 58%, P = 0.15). Final IOP was lower with randomization to trabeculectomy (16.3 ± 5.1 mmHg) than medication (18.8 ± 6.7 mmHg, P < 0.0001). In regression models, randomization to trabeculectomy (P < 0.0001) was associated with lower IOP, and simultaneous trabeculectomy and cataract surgery was associated with higher IOP (P = 0.008) than trabeculectomy alone. Subjects receiving Phaco/IOL had significantly better final acuity (P < 0.0001) and visual function (P = 0.035), despite concurrent glaucoma treatment. Final visual acuity was worse in those receiving trabeculectomy in addition to cataract surgery, but this was of borderline significance (P = 0.06). CONCLUSIONS: Trabeculectomy lowered IOP significantly more than medical treatment, but with slightly greater loss of visual acuity. Combined phaco/IOL and trabeculectomy improved visual acuity with substantial IOP lowering.

A study of the spectrum of Acanthamoeba keratitis: a three-year study at a tertiary eye care referral center in South India.

PURPOSE: To determine the epidemiological and clinical characteristics of Acanthamoeba keratitis and also to determine the sensitivity and specificity of smears in the detection of Acanthamoeba. MATERIALS AND METHODS: A retrospective review of all culture-positive cases of Acanthamoeba keratitis seen between October 1999 and August 2002 was performed. Corneal scrapes were subjected to culture and microscopy using standard protocols. RESULTS: Out of 3183 consecutive patients with clinically diagnosed corneal ulcers evaluated, 33 (1.04%) were found to be due to Acanthamoeba. Twenty-four out of 33 (72.72%) were less than 51 years of age (P<0.001). All patients were from rural areas (P<0.001) and 26 (78.79%) of them were agricultural workers (P=0.031). All 33 had history of corneal injury (P<0.001) and 28 (84.85%) patients had injury with mud (P<0.001). All 33 (100%) patients had previous medical treatment (P=0.009) and 10 (30.3%) had used traditional eye medicines (P=0.183). A clinical pattern of ring infiltrate was characteristic in 15 (45.45%) patients. The diameter of the corneal ulcer was more than 6 mm in 27 (81.82%) eyes (P<0.001). Twenty-six (78.79%) patients had visual acuity of perception of light on initial presentation (P<0.001) and 24 (72.73%) had the same as their final visual outcome. The sensitivity of 10% potassium hydroxide (KOH) preparation was found to be higher (P<0.001) in the detection of Acanthamoeba cysts. CONCLUSION: The incidence of Acanthamoeba keratitis amongst the corneal ulcer patients was 1% in this setting and it was mainly due to corneal injury by mud. The KOH preparation is a sensitive diagnostic tool for the detection of Acanthamoeba. Delayed diagnosis or misdiagnosis and inappropriate antimicrobial therapy results in poor visual outcome.

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease.

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.

Gallbladder Na+/H+ exchange activity is up-regulated prior to cholesterol crystal formation.

BACKGROUND: Gallbladder Na+ and H2O absorption are increased prior to gallstone formation and may promote cholesterol nucleation. Na+/H+ exchange (NHE) isoforms NHE2 and NHE3 are involved in gallbladder Na+ transport in prairie dogs. We examined whether increased gallbladder Na+ absorption observed during early gallstone formation is the result of NHE up-regulation. MATERIALS AND METHODS: Native gallbladder and primary cultures of gallbladder epithelial cells (GBECs) harvested from prairie dogs fed nonlithogenic (CON) or 1.2% cholesterol diet for varying lengths of time to induce cholesterol-saturated bile (PreCRYS), cholesterol crystals (CRYS), or gallstones (GS) were used. NHE activity was assessed by measuring dimethylamiloride-inhibitable 22Na+ uptake under H+ gradient in primary GBECs. HOE-694 was used to determine NHE2 and NHE3 contributions. NHE protein and mRNA expression were examined by Western and Northern blots, respectively. RESULTS: Gallbladder total NHE activity was 25.1 +/- 1.3 nmol mg protein(-1) min(-1) in the control and increased during gallstone formation peaking at the PreCRYS stage (98.4 +/- 3.9 nmol mg protein(-1) min(-1)). There was a shift in NHE activity from NHE2 to NHE3 as the animals progressed from no stones through the PreCRYS and CRYS stages to gallstones. The increase in NHE activity was partly caused by an increased Vmax without any change in K(Na)m. Both NHE2 and NHE3 protein increased moderately during the PreCRYS stage without increases in mRNA expression. CONCLUSIONS: Increased gallbladder Na+ absorption observed prior to crystal formation is in part caused by an increase NHE activity which is not fully accounted for by an increase in NHE proteins and mRNA levels but may be explained by enhanced localization in the membranes and/or altered regulation of NHE.

Risk factors for age related cataract in a rural population of southern India: the Aravind Comprehensive Eye Study.

AIM: To determine risk factors for lens opacities and age related cataract in an older rural population of southern India. METHODS: A cross sectional population based study of 5150 people aged 40 years and above from 50 clusters from three districts in southern India. The lens was graded and classified after dilation using LOCS III system at the slit lamp for cataract. Definite cataract was defined as nuclear opalescence >/=3.0 and/or cortical cataract >/=3.0 and/or PSC >/=2.0. RESULTS: Definite cataracts were found in 2449 (47.5%) of 5150 subjects and the prevalence of cataract increased with age. The age adjusted prevalence of cataract was significantly lower in males (p = 0.0002). Demographic risk factors-increasing age and illiteracy-were common for the three subtypes of cataract; females were more likely to have cortical cataracts and nuclear cataracts. Additionally, nuclear cataracts were associated with moderate smoking (OR:1.28, 95% CI:1.01 to 1.64), lean body mass indices (OR: 1.37, 95% CI: 1.17 to 1.59) and higher waist to hip ratios (OR: 0.67, 95% CI: 0.54 to 0.82); cortical cataracts with hypertension (OR: 1.39 95% CI:1.11 to 1.72), pseudoexfoliation (OR:1.53,95% CI:1.17 to 2.01), and moderate to heavy smoking; and posterior subcapsular cataracts with diabetes (OR:1.55, 95% CI:1.12 to 2.15), lean body mass (OR:1.32, 95% CI:1.11 to 1.57), and high waist to hip ratios (OR: 0.77, 95% CI: 0.62 to 0.94). CONCLUSIONS: Risk factors for age related cataract in this population do not appear to be different from those reported in other populations. Further studies are required to identify the reason for the high prevalence of age related cataract and to understand better the role of each risk factor for cataractogenesis in this population.

Functional characterization of Na(+)/H(+) exchangers in primary cultures of prairie dog gallbladder.

Gallbladder Na(+) absorption is linked to gallstone formation in prairie dogs. We previously reported Na(+)/H(+) exchanger (NHE1-3) expression in native gallbladder tissues. Here we report the functional characterization of NHE1, NHE2 and NHE3 in primary cultures of prairie dog gallbladder epithelial cells (GBECs). Immunohistochemical studies showed that GBECs grown to confluency are homogeneous epithelial cells of gastrointestinal origin. Electron microscopic analysis of GBECs demonstrated that the cells form polarized monolayers characterized by tight junctions and apical microvilli. GBECs grown on Snapwells exhibited polarity and developed transepithelial short-circuit current, I(sc), (11.6 +/- 0.5 microA. cm(-2)), potential differences, V(t) (2.1 +/- 0.2 mV), and resistance, R(t) (169 +/- 12 omega. cm(2)). NHE activity in GBECs assessed by measuring dimethylamiloride-inhibitable (22)Na(+) uptake under a H(+) gradient was the same whether grown on permeable Snapwells or plastic wells. The basal rate of (22)Na(+) uptake was 21.4 +/- 1.3 nmol x mg prot(-1) x min(-1), of which 9.5 +/- 0.7 (approximately 45%) was mediated through apically-restricted NHE. Selective inhibition with HOE-694 revealed that NHE1, NHE2 and NHE3 accounted for approximately 6%, approximately 66% and approximately 28% of GBECs' total NHE activity, respectively. GBECs exhibited saturable NHE kinetics ( V(max) 9.2 +/- 0.3 nmol x mg prot(-1) x min(-1); K(m) 11.4 +/- 1.4 m M Na(+)). Expression of NHE1, NHE2 and NHE3 mRNAs was confirmed by RT-PCR analysis. These results demonstrate that the primary cultures of GBECs exhibit Na(+) transport characteristics similar to native gallbladder tissues, suggesting that these cells can be used as a tool for studying the mechanisms of gallbladder ion transport both under physiologic conditions and during gallstone formation.

Frequency-doubled Nd:YAG laser treatment for premacular hemorrhage.

BACKGROUND AND OBJECTIVE: Premacular hemorrhage occurs as a result of Valsalva retinopathy, proliferative diabetic retinopathy, and retinal artery macroaneurysm and may cause sudden, profound visual loss. Currently, it is managed with observation or vitrectomy. An alternative method of treatment is by Nd:YAG laser or argon laser membranotomy. This study investigates the efficacy of frequency-doubled Nd:YAG laser membranotomy. PATIENTS AND METHODS: Twelve patients had frequency-doubled Nd:YAG laser membranotomy as a two-step procedure to drain premacular hemorrhage: two stretch burns to make the membrane stable and taut and then placement of penetration burns between stretch burns. The follow-up period was 18 months. RESULTS: Ten eyes had marked clearing of hemorrhage and immediate improvement of vision following the laser treatment. One eye with retinal macroaneurysm and another with proliferative diabetic retinopathy did not show marked improvement immediately following membranotomy. CONCLUSION: Frequency-doubled Nd:YAG membranotomy is a safe, simple, and noninvasive alternative to conservative treatment or vitrectomy and allows faster resolution of premacular hemorrhage.

Nocardia asteroides keratitis in south India.

PURPOSE: To determine the risk factors, microbiological features, clinical features and other epidemiological characteristics of Nocardia keratitis seen at a tertiary eye care centre in south India. METHODS: We evaluated 31 patients with Nocardia keratitis seen over two years, from September 1999 to September 2001. Corneal scrapings were subjected to microscopy and culture using standard protocols. RESULTS: Out of 2184 corneal ulcers cultured, 31(1.42%) were found to be Nocardia asteroides. All 31(100%) were detected correctly by 10% potassium hydroxide wet mount preparation. The highest percentage of isolates was susceptible to gentamicin(100%) followed by ciprofloxacin(93.55%). Twenty four (77.42%) patients were from rural areas; 22(70.97%) were agricultural workers; 29(93.55%) had history of trauma; 2(6.45%) had previous ocular surgery; 28(90.32%) had ocular injury with soil and sand; and 22(70.97%) had ocular injury while working in the agricultural fields. Ten (32.26%) patients presented at our institute between 15 to 35 days of onset of illness, 26(83.87%) had previous medical treatment, and 15(48.39%) patients had used traditional eye medicines. The average age of the patients was 46.16 years, with a range of 11 to 75 years. No seasonal variation was observed. CONCLUSIONS: A high index of suspicion of Nocardia infection should exist in patients with a history of trauma to the eye by soil or sand. The organisms are sensitive to commonly used topical ocular antibiotics.

A population based eye survey of older adults in Tirunelveli district of south India: blindness, cataract surgery, and visual outcomes.

AIMS: To assess the prevalence of vision impairment, blindness, and cataract surgery and to evaluate visual acuity outcomes after cataract surgery in a south Indian population. METHODS: Cluster sampling was used to randomly select a cross sectional sample of people > or =50 years of age living in the Tirunelveli district of south India. Eligible subjects in 28 clusters were enumerated through a door to door household survey. Visual acuity measurements and ocular examinations were performed at a selected site within each of the clusters in early 2000. The principal cause of visual impairment was identified for eyes with presenting visual acuity <6/18. Independent replicate testing for quality assurance monitoring was performed in subjects with reduced vision and in a sample of those with normal vision for six of the study clusters. RESULTS: A total of 5795 people in 3986 households were enumerated and 5411 (93.37%) were examined. The prevalence of presenting and best corrected visual acuity > or =6/18 in both eyes was 59.4% and 75.7%, respectively. Presenting vision <6/60 in both eyes (the definition of blindness in India) was found in 11.0%, and in 4.6% with best correction. Presenting blindness was associated with older age, female sex, and illiteracy. Cataract was the principal cause of blindness in at least one eye in 70.6% of blind people. The prevalence of cataract surgery was 11.8%-with an estimated 56.5% of the cataract blind already operated on. Surgical coverage was inversely associated with illiteracy and with female sex in rural areas. Within the cataract operated sample, 31.7% had presenting visual acuity > or =6/18 in both eyes and 11.8% were <6/60; 40% were bilaterally operated on, with 63% pseudophakic. Presenting vision was <6/60 in 40.7% of aphakic eyes and in 5.1% of pseudophakic eyes; with best correction the percentages were 17.6% and 3.7%, respectively. Refractive error, including uncorrected aphakia, was the main cause of visual impairment in cataract operated eyes. Vision <6/18 was associated with cataract surgery in government, as opposed to that in non-governmental/private facilities. Age, sex, literacy, and area of residence were not predictors of visual outcomes. CONCLUSION: Treatable blindness, particularly that associated with cataract and refractive error, remains a significant problem among older adults in south Indian populations, especially in females, the illiterate, and those living in rural areas. Further study is needed to better understand why a significant proportion of the cataract blind are not taking advantage of free of charge eye care services offered by the Aravind Eye Hospital and others in the district. While continuing to increase cataract surgical volume to reduce blindness, emphasis must also be placed on improving postoperative visual acuity outcomes.

Gangrenous Richter's hernia with intrasac abscess.

A 43 year old female was admitted with features of intestinal obstruction. On laparotomy, a strangulated Richter's hernia with an abscess within an incisional hernial sac through a previous lower segment caesarean section scar was diagnosed. Resection and anastomosis was performed. Strangulated Richter's hernia is a rare entity making up 8.3% of all strangulated hernias. There have been reports of Richter's hernia with strangulation in inguinal hernia, femoral hernia and port hernia after laparoscopic surgery but none so far in an incisional hernia.

Vitamin E kinetics in smokers and nonsmokers.

Does cigarette smoking increase vitamin E utilization in vivo? A trial was carried out in 6 smokers and 5 nonsmokers of comparable ages and serum lipids. Subjects consumed 75 mg each d(3)-RRR and d(6)-all rac-alpha-tocopheryl acetates (natural and synthetic vitamin E, respectively) daily for 7 d with a standardized breakfast. Fasting blood samples were drawn on days -7, -6, -5, -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 6, 7, 9, 14, 21 (negative days indicate supplementation). In both groups, plasma d(3)-alpha-tocopherol concentrations were approximately double of d(6)-alpha-tocopherol. At day 0, the %d(3) alpha-tocopherols (d(3)-alpha-tocopherol/total-alpha-tocopherol x 100) were similar in both smokers and nonsmokers. Subsequently, there was a trend toward a faster exponential disappearance of the plasma %d(3) alpha-tocopherol in smokers compared with nonsmokers (0.30 +/- 0.04 compared with 0.24 +/- 0.05, p =.0565). The calculated %d(3) half-lives were 55.6 +/- 7.4 h in smokers and 72.1 +/- 17.3 h in nonsmokers (p =.0630). By day 21, the %d(3) in smokers had decreased to 1.4% +/- 0.3% while it was 2.2% +/- 0.7% (p =.0418) in the nonsmokers. These data suggest that smoking increases plasma vitamin E disappearance, but further studies are needed to confirm this finding and to assess its cause.