New algorithm for toric intraocular lens power calculation considering the posterior corneal astigmatism.

PURPOSE: To assess the accuracy of toric intraocular lens (IOL) power calculations of a new algorithm that incorporates the effect of posterior corneal astigmatism (PCA). SETTING: Abbott Medical Optics, Inc., Groningen, the Netherlands. DESIGN: Retrospective case report. METHODS: In eyes implanted with toric IOLs, the exact vergence formula of the Tecnis toric calculator was used to predict refractive astigmatism from preoperative biometry, surgeon-estimated surgically induced astigmatism (SIA), and implanted IOL power, with and without including the new PCA algorithm. For each calculation method, the error in predicted refractive astigmatism was calculated as the vector difference between the prediction and the actual refraction. Calculations were also made using postoperative keratometry (K) values to eliminate the potential effect of incorrect SIA estimates. RESULTS: The study comprised 274 eyes. The PCA algorithm significantly reduced the centroid error in predicted refractive astigmatism (P < .001). With the PCA algorithm, the centroid error reduced from 0.50 @ 1 to 0.19 @ 3 when using preoperative K values and from 0.30 @ 0 to 0.02 @ 84 when using postoperative K values. Patients who had anterior corneal against-the-rule, with-the-rule, and oblique astigmatism had improvement with the PCA algorithm. In addition, the PCA algorithm reduced the median absolute error in all groups (P < .001). CONCLUSIONS: The use of the new PCA algorithm decreased the error in the prediction of residual refractive astigmatism in eyes implanted with toric IOLs. Therefore, the new PCA algorithm, in combination with an exact vergence IOL power calculation formula, led to an increased predictability of toric IOL power.

Clinical Profile and Laboratory Parameters in 1051 Victims of Snakebite from a Single Centre in Kerala, South India.

INTRODUCTION: Snakebite is an occupational hazard causing considerable morbidity and mortality worldwide, particularly so in tropical countries like India. OBJECTIVE: The aim of this study is to (i) review the demographic, clinical and laboratory findings in patients (1051) admitted with venomous snakebite (ii) to correlate mortality, morbidity and duration of hospital stay with clinical signs, symptoms and laboratory parameters. METHODS: A retrospective study of 1051 patients treated for snakebite over 10 years (2000 - 2009) in Little Flower Hospital, Angamaly, Kerala. RESULTS: Of the 1051 cases, haemotoxic bites outnumbered 586 (56%) neurotoxic ones 435 (41%). Most victims were males 706 (70%), 792 (75%) of the victims were between 20-60 years of age, lower limb bites predominated, 883 (84%). Among laboratory tests, haemoconcentration (>15 gm/dl), low platelets (<100,000 cmm), proteinuria (3+), raised creatinine (>4 mg/dl) and elevated d-Dimer (>200 µg/ml) were associated with an adverse prognosis. Major complications include death in 38 (3.6%) victims, Acute Respiratory Distress Syndrome 20 (1.9%), Acute Renal Failure 220 (20.9%), needing haemodialysis in 110 (10.4%). Ventilator support was needed in 41 (3.9%) victims and gangrene was seen in 43 (4%). 891 (85%) patients received ASV with adverse reactions in 379 (37%) with 3 having anaphylaxis. The mean dose of antivenom given for neuroparalytic snakebite was 12.26 vials (range 0-32) and 16.79 vials (range 2-52) for hemotoxic bites. 45% of the victims had a hospital stay of <5 days, 40% between 6-14 days and 15% victims of >15 days. CONCLUSIONS: This study highlights that snakebite is an occupational hazard, and the time between bite and treatment determines the prognosis. The low mortality observed in our study is probably due to early admission to hospital, early and adequate ASV administration and better management of complications. The study also indicates that the use of PT and APTT tests along with 20 min WBCT, helped in initiating early treatment. Symptoms of abdominal pain, vomiting, local excruciating pain at the bite site with regional lymphadenopathy even before the prolongation of the clotting time was taken as a sign of systemic envenomation. In the absence of a diagnostic kit, a definite protocol for treatment of snakebite has to be devised. ABBREVIATIONS: Intensive Care Unit (ICU); Polyvalent Anti-snake venom (ASV); whole blood clotting test (WBCT); Acute Respiratory Distress Syndrome (ARDS) ; Acute Kidney Injury(AKI); Disseminated Intravascular Coagulation (DIC); Anterior Wall myocardial infarction (AMI); Cerebro-Vascular Accidents (CVA).

Functional Radionuclide Imaging, In-Vitro Radioiodine Uptake Estimation and RT-PCR in the Evaluation of Sodium Iodide Symporter (NIS) Expression and Functionality in Breast Cancer: A Pilot Study.

Breast cancer is a common malignancy in females, which is considered as a systemic disease, whose treatment involves combined modality including systemic as well as local treatment. Recent studies have shown that breast cancer also expresses Sodium Iodide Symporter (NIS) gene, like in the thyroid, which is the factor responsible for the uptake of iodide by the thyroid, enabling radioiodine therapy of thyroid disorders. This study aimed to evaluate various radionuclide imaging characteristics, in vitro radioiodine uptake (RAIU) and evaluation of NIS expression by using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) to explore sodium iodide symporter (NIS) expression and iodine uptake in breast cancer and to explor e whether radioiodine can be used for the diagnosis and treatment of breast cancer. Ways of differential regulation of NIS expression in breast cancer has also been explored. Female patients with palpable breast lump and histologically proven infiltrating duct carcinoma were taken up for the study, which included 50 females of mean age 49 years. (range: 23-73 years). The patients were categorized into different groups, depending on the type of the study performed. The uptake patterns in various imaging modalities were analyzed and compared with invitro and RT-PCR studies. 68 % of breast cancer cases showed (99m)Tc-pertechnetate uptake at the initial images. This finding could partly be due to tumor vascularity, which is usually higher compared to the normal tissues. The uptake in the delayed imaging could be related to that due to NIS in the breast. Use of perchlorate or stable iodine did not alter the pertechnetate uptake pattern in breast tumor. Good correlation between (99m)Tc-pertechnetate and (99m)Tc-tetrofosmin uptake in breast cancer was demonstrated. In vitro radioactive iodine uptake in the breast tumor was significantly higher than that in the normal breast tissue. Only 42 % of breast tumor samples studied using RT-PCR showed NIS expression. Correlation between (99m)Tc-pertechnetate uptake and NIS expression could not be well established. Further studies with higher dose of radioiodine and/or mechanisms of differentially blocking the thyroid are required to assess the feasibility of radioiodine therapy for breast cancer.

Programmatic management of multidrug-resistant tuberculosis: models from three countries.

BACKGROUND: Although multidrug-resistant tuberculosis (MDR-TB) is a major global health problem, there is a gap in programmatic treatment implementation. METHODS: This study describes MDR-TB treatment models in three countries--Peru, Russia and Lesotho-- using qualitative data collected over a 13-year period. RESULTS: A program analysis is presented for each country focusing on baseline medical care, initial implementation and program evolution. A pattern analysis revealed six overarching themes common to all three programs: 1) importance of baseline assessments, 2) early identification of key collaborators, 3) identification of initial locus of care, 4) minimization of patient-incurred costs, 5) targeted interventions for vulnerable populations and 6) importance of technical assistance and funding. Site commonalities and differences in each of these areas were analyzed. CONCLUSIONS: It is recommended that all programs providing MDR-TB treatment address these six areas during program development and implementation.

Anterior segment optical coherence tomography for transepithelial phototherapeutic keratectomy in central corneal stromal scarring.

PURPOSE: To demonstrate the use of anterior segment optical coherence tomography (ASOCT) in planning phototherapeutic keratectomy (PTK) removal of central corneal stromal scarring. METHODS: A 62-year-old male presented with central corneal scars associated with significant ocular surface disease. Videokeratographies obtained using 3 different systems were not reliable. ASOCT, however, provided consistent pachymetry in the presence of noncalcific stromal opacity, which extended below Bowman membrane. PTK was performed with a transepithelial ablation, mitomycin C (MMC), and a slightly myopic photorefractive keratectomy. RESULTS: Slit-lamp examination and postoperative ASOCT revealed an optically clear cornea with no evidence of stromal haze at any time point. CONCLUSION: Transepithelial PTK guided by ASOCT can allow for the precise and accurate removal of central corneal stromal opacities, resulting in a favorable refractive outcome.

Infliximab for the treatment of refractory progressive sterile peripheral ulcerative keratitis associated with late corneal perforation: 3-year follow-up.

PURPOSE: To report a case of refractory progressive sterile peripheral ulcerative keratitis (PUK) that resulted in late corneal perforation, despite good initial response to tumor necrosis factor-alpha inhibitor infliximab. METHODS: Review of the clinical course of a patient with progressive PUK treated with infliximab infusions of 3 mg/kg intravenously. RESULTS: A 72-year-old man presented with a visual acuity of 20/200 and a 5-month history of a progressive sterile PUK. More than 90% of the surface area previously unresponsive to 8 weeks of high-dose systemic steroid therapy healed within 1 week of the first infusion. After his second infusion, best-corrected visual acuity improved to 20/30(+2), with 2 small epithelial defects remaining. However, the remaining unhealed cornea thinned to an area of microperforation 6 weeks after his third dose, prompting an increase in dose frequency to every 4 weeks. One month after his fifth infusion, the area of ulceration healed completely. After his seventh infusion, the patient developed a deep venous thrombosis and infliximab was discontinued. After 10 months of remission, clear corneal cataract surgery was performed. Three years after initial presentation, he remains in remission with a corrected visual acuity of 20/20. CONCLUSIONS: Infliximab was effective in rapidly arresting the progression of a sterile PUK in our patient. Optimal dosing for infliximab in PUK has not been established, and increasing dose frequency to every 4 weeks may be necessary. Despite a progressive PUK resulting in corneal perforation, treatment with infliximab and subsequent visual rehabilitation can result in sustained remission and an excellent visual outcome.

Simple method for accurate alignment in toric phakic and aphakic intraocular lens implantation.

A simple technique for the accurate surgical alignment of toric phakic and aphakic intraocular lenses (IOLs) is described. The mathematical relationship between toric misalignment and cylinder error is reviewed to demonstrate the importance of toric lens alignment in the setting of increased rotational stability with newer generation lenses. A formula for calculating the exact lens misalignment given a manifest cylinder is also presented.

Calculating the optimal rotation of a misaligned toric intraocular lens.

PURPOSE: To present a formula for calculating the theoretical optimal position of a toric intraocular lens (IOL) that is rotationally misaligned. SETTING: Private practice in an academically affiliated setting. METHODS: Using equations for astigmatic decomposition, a formula to calculate the optimal rotation of an implanted toric IOL requiring only the power and axis of the IOL and the total eye astigmatism was derived. RESULTS: The optimal rotational position can be obtained from the derivation. CONCLUSION: The formula calculates the rotation an implanted toric IOL must undergo to minimize an eye's manifest astigmatism.

Trends in resistance to ciprofloxacin, cefazolin, and gentamicin in the treatment of bacterial keratitis.

PURPOSE: The aim of this study was to evaluate the microbial profile, resistance patterns, and antibiotic sensitivity of bacterial keratitis to three commonly used ocular antibiotics. METHODS: All cases of bacterial keratitis referred to the Massachusetts Eye and Ear Infirmary Microbiology Laboratory from two consecutive annual 10-month periods were reviewed. The bacterial profile and resistance to ciprofloxacin, cefazolin, and gentamicin was evaluated within the two intervals. RESULTS: Of the 485 cultures analyzed, 66.4% (322) were positive for bacterial isolates. Of these, 19.2% were polymicrobial, 87.5% were gram-positive, and 12.5% were gram-negative. The most prevalent isolate was coagulase-negative Staphylococcus (45.5%), followed by S. aureus (15.2%). The resistance patterns for gram-positive bacteria for ciprofloxacin for the first versus second time interval were 12% and 22% (P = 0.04) respectively, for cefazolin 13% and 23% (P = 0.04), and for gentamicin 4% and 7% (P = 0.36). The resistance patterns for gram-negative bacteria for ciprofloxacin, cefazolin, and gentamicin were not significantly different in the two tested time periods (all P > 0.05). CONCLUSIONS: There was increased resistance of gram-positive organisms to ciprofloxacin and cefazolin, but not gentamicin, in the two examined time periods. Increased resistance to these commonly used antibiotics emphasizes the need for close follow-up after initial empiric treatment, and maintaining a low threshold for selecting alternative therapy.

Improved case detection of active tuberculosis associated with an antiretroviral treatment program in Lesotho.

Tuberculosis (TB) remains the leading infectious killer of adults with human immunodeficiency virus (HIV) globally. Lesotho has the third highest prevalence of HIV and the fourth highest prevalence of TB worldwide, and the majority of TB patients are co-infected with HIV. This paper describes an antiretroviral treatment (ART) program instituted in a health center in a mountain region of Lesotho. Although the main goal of the program was to increase HIV detection and initiate ART for patients, the program also resulted in a ten-fold increase in the detection of TB among patients with and without HIV.

First authenticated cases of life-threatening envenoming by the hump-nosed pit viper (Hypnale hypnale) in India.

In Kerala, south-western India, five patients developed systemic envenoming after bites by hump-nosed pit vipers (Hypnale hypnale), proved by identification of the snakes responsible. Two of the dead snakes had been misidentified as saw-scaled vipers (Echis carinatus), while three had remained unidentified. Symptoms of local envenoming were pain, swelling, haemorrhagic blistering, bruising and regional lymphadenopathy. Systemic symptoms included headache, nausea, vomiting and abdominal and chest pain. There was evidence of haemostatic dysfunction (coagulopathy, fibrinolysis, thrombocytopenia or spontaneous systemic haemorrhage) in all cases and of microangiopathic haemolysis in two. Two patients were haemodialysed for acute renal failure, one of whom developed pulmonary oedema requiring mechanical ventilation. In India, H. hypnale has not previously been regarded as a cause of frequent or potentially dangerous envenoming. Its medical importance has been overlooked throughout its geographical range, probably because of confusion with other small species. No specific antivenom exists, yet most patients are treated with non-specific antivenoms, risking reactions without hope of benefit. An effective antivenom is urgently needed in south India and in Sri Lanka, where this species is also a common cause of bites.

Clinical and programmatic considerations in the treatment of MDR-TB in children: a series of 16 patients from Lima, Peru.

SETTING: Since 2000, the directly observed treatment, short-course (DOTS) strategy has been expanded in several countries to include treatment of multidrug-resistant tuberculosis (MDR-TB). This strategy is known as DOTS-Plus. Tuberculosis is a common cause of morbidity and mortality for children throughout the developing world. Children may also be infected with MDR-TB, yet most developing countries do not specifically address pediatric MDR-TB. OBJECTIVE: To present the intermediate outcomes of the first 16 children enrolled in the Peruvian DOTS-Plus program and to demonstrate the tolerability of second-line anti-tuberculosis drugs. RESULTS: Three children completed therapy and are cured, one child had bacteriologic and clinical failure after 12 months of therapy and died of respiratory insufficiency, and 12 have intermediate outcomes demonstrating favorable clinical, bacteriologic, and radiographic evidence of improvement after 9-19 months of therapy. CONCLUSIONS: Of the 16 pediatric DOTS-Plus patients, 15 have tolerated therapy well and have had favorable clinical evolution. However, the diagnosis of pediatric MDR-TB is often extremely delayed due to reliance on the adult case definition and should be changed to prevent progressive, chronic illness in such children. Programmatic changes could facilitate earlier diagnosis and treatment of pediatric MDR-TB in Peru and in other DOTS-Plus programs.

Contact lenses for the treatment of pediatric cataracts.

OBJECTIVE: To evaluate the experiences, attitudes, and perceptions of the caregivers of children with cataracts who were visually rehabilitated with contact lenses. PARTICIPANTS: One hundred twenty-three caregivers of children <8.1 years old treated for unilateral and bilateral cataracts at one pediatric hospital. DESIGN: Survey by questionnaire. INTERVENTION: Primary caregivers were asked to complete an anonymous questionnaire. MAIN OUTCOME MEASURES: Caregiver responses to questions assessing background and demographic and clinical information, as well as perceptions, attitudes, levels of compliance, and anxiety with respect to treatment, were reviewed. Caregivers were also asked to choose between aphakic rehabilitation with contact lenses, aphakic glasses, or intraocular lenses, given various hypothetical scenarios differing in regard to their final visual prognosis, risks of treatment complications, and cost. RESULTS: The response rate was 82.9%. Absolute average stress levels for contact lens use were 1.36 +/- 1.79 and 0.79 +/- 1.48 (scale, 0-5) for insertion and removal, respectively, compared with 4.03 +/- 1.64 and 2.40 +/- 1.92 for cataract surgery and patching therapy, respectively. Although average paired initial resistance to treatment (RT) levels for contact lens insertion and removal on a scale of 0 to 3 were high (2.09 +/- 1.15) and moderate (1.63 +/- 1.20), respectively, final RT levels were significantly lower (1.09 +/- 1.14 and 0.66 +/- 1.07, respectively; P < 0.0001). The vast majority of caregivers chose contact lens use in hypothetical scenarios that depicted realistic expectations for other forms of aphakic rehabilitation. CONCLUSIONS: In our study, contact lenses seemed to be well tolerated by most patients, as assessed by caregivers. Although initial resistance to contact lens use is high, this decreases with time. Relative to other events in the treatment of pediatric cataracts, contact lens use is not a major stressor for most caregivers and patients. This study supports the notion that contact lenses should continue to receive serious consideration as a treatment option for pediatric cataracts.

Mechanisms of corneal ulceration.

Corneal ulceration is a significant cause of visual morbidity. Although this discussion has primarily focused on the local factors involved in non-immune related sterile corneal ulcerations, an understanding of these mechanisms is important since a final common pathway that is conceivably relevant to all forms of corneal ulceration exists. With respect to the treatment of chronic sterile ulcerations, our contemporary armamentarium is extensive; an acknowledgement to the inadequacies of any single strategy. A sound appreciation of the subtleties involved in the pathogenesis of corneal ulceration and the orchestration of wound repair will lead us towards more effective strategies to decrease inflammation associated with ulceration, promote corneal wound healing, and ultimately provide better care for our patients.

Pilot study of formestane in postmenopausal women with breast cancer.

A pilot study of Formestane or 4-Hydroxyandrostenedione (Lentaron), a new endocrine agent, was conducted on 18 postmenopausal patients with locally advanced and metastatic breast cancer. 16 patients were evaluable for response and objective responses were seen in 4 patients (25%). Stabilisation of disease was seen in 5 patients (32%). Out of 17 patients evaluable for toxicity, 3 (18%) reported adverse effects including hot flushes, lethargy and myalgia. Adverse effects were mild, transient and no patient required discontinuation of drug. Our study confirms that Formestane is a well tolerated endocrine agent with low toxicity and reasonable efficacy in postmenopausal patients with locally advanced and metastatic breast cancer.

Induced alterations in calcium uptake rate in normoxic rate proximal tubules.

This study is well-oxygenated, freshly isolated rat proximal tubules (RPT), examined the effects of several drugs that alter the transmembrane K+ and Na+ gradients across cell membranes, including valinomycin (VAL), amphotericin B (AMPHO), and ouabain (OUAB). The effects of high extracellular potassium chloride (KCl) concentrations (45 mM) and low extracellular sodium concentration (100mM) were also studied. After 10 min of drug exposure Ca2+ uptake rate (nmol/mg/min) increased from 2.7 to 3.8 with VAL (p < .02), from 2.9 to 3.7 with AMPHO (p < .05), from 3.6 to 4.1 with OUAB (p < .05), and from 3.2 to 4.8 with 45 mM KCl (p < .001). Ca2+ uptake rate was sustained at these high levels at 20 min in all treated RPT except those exposed to OUAB. LDH release averaged less than 15% in control tubules and did not increase significantly except in RPT treated with VAL, where LDH release at 10 min was 48% and at 20 min was 57% (both p < .001). Of importance, only in VAL-treated RPT did ATP decrease to low levels (6.7 nmol/mg in control to 2.0 +/- 0.3 nmol/mg in VAL, p < .001). Treatment with verapamil reduced Ca2+ uptake rates at 10 min in VAL-treated RPT (from 3.8 to 3.1, p < .02, in AMPHO-treated RPT (from 3.8 to 3.1 p < .001), in OUAB-treated tubules (from 4.0 to 3.4, p < .01), and in KCl-treated RPT (from 3.7 to 3.2, p < .01). These results indicate that acute changes in the transmembrane ion gradient in RPT are accompanied by increased Ca2+ uptake rates. Ca2+ uptake rates are also increased during O2 deprivation in RPT, a situation in which the transmembrane ion gradient is likewise altered. The increased Ca2+ uptake rate observed in the present study and during hypoxia may have a common basis, that is, altered transmembrane ion gradients or some function thereof.

Lithium toxicity--a risk factor for neuroleptic malignant syndrome.

We report a case of neuroleptic malignant syndrome (NMS). Lithium toxicity might have predisposed to the development of the syndrome in our patient. The patient had hyperthermia, extrapyramidal rigidity, disturbance in autonomic function and raised serum CPK level.

A novel method of inducing and assuring total anoxia during in vitro studies of O2 deprivation injury.

Oxyrase is an enzyme mixture coveted by microbiologists for its unique ability to remove O2 from media in which anaerobic bacteria are grown. The study reported here examined the potential usefulness of Oxyrase as an adjunct to gassing freshly isolated rat proximal tubules (RPT) with 95% N2-5% CO2 in an attempt to achieve totally O2-free conditions (anoxia) before initiating studies on the mechanism of O2 deprivation injury in vitro. RPT, in 6 ml of Krebs-Henseleit buffer (KHB), were initially gassed with 95% N2-5% CO2 at 1.5 liters/min for 5 min and incubated for 15 to 30 min at 37 degrees C in a shaking water bath, pO2 decreased from approximately 400 to 80 mm Hg. If RPT were present in the KHB, pO2 was even lower, i.e., approximately 50 mm Hg. Addition of increasing concentrations of Oxyrase (300 to 1,500 mU) to KHB alone, that is, without RPT, reduced pO2 from 80 mm Hg to less than 5 mm Hg; increasing the gas rate from 1.5 to 3.0 liter/min of 95% N2-5% CO2, the concentration of Oxyrase to 1,800 mU, and adding RPT reduced pO2 to zero. In this latter condition, pO2 remained unmeasurable during the 20 min of study and neither pH nor pCO2 changed compared with control values. Oxyrase (1,800 mU) had no effect on lactate dehydrogenase release, a sign of membrane injury, in normoxic RPT in KHB. We conclude that anoxia can easily be achieved by the addition of Oxyrase to KHB in which RPT are suspended, if the appropriate concentration of Oxyrase is added and if the RPT are gassed with 95% N2-5% CO2. This concentration of Oxyrase exerts no detrimental effects on RPT gassed with 95% O2-5% CO2.