Search

In a search for geochemical factors that could play a role in the pathogenesis of tropical endomyocardial fibrosis, endomyocardial tissue samples obtained from patients at necropsy or operation were analysed for major elements present in laterite and monazite, which are important soil constituents of Kerala State of India. Atomic absorption spectrophotometry was used for detecting iron, silicon, aluminium, zinc, magnesium, calcium, sodium, potassium, and manganese and neutron activation analysis for thorium. Compared with control samples from victims of fatal accidents, an excess of thorium, sodium, and calcium and a deficiency of magnesium were present in samples from patients. It has been shown earlier that the staple diets of people in Kerala have high concentrations of thorium, and these data show that thorium can become concentrated in cardiac tissues. It is speculated that thorium excess in conjunction with magnesium deficiency may play a role in the causation of tropical endomyocardial fibrosis. [ABSTRACT FROM PUBLISHER]

Purpose: It has been observed that the area under the free carboplatin concentration in plasma ultrafiltrate versus time curve (AUC) is related to toxicity and tumour response. For this reason, it can be important to measure the carboplatin AUC and subsequently adjust the dose to achieve a predefined target AUC. The use of limited sampling strategies enables relatively simple measurement and calculation of actual carboplatin AUCs.Methods: We studied the performance of a limited sampling model, based on a single 24-h sample (the Ghazal-Aswad model). in 52 patients who received carboplatin in two different chemotherapy regimens (a carboplatin-paclitaxel combination and a high-dose carboplatin-thiotepa-cyclophosphamide combination).Results: The measured mean AUC in our population was 4.1 min x mg/ml (median 3.9, range 1.9 6.3, SD 1.0 min x mg/ml). With the limited sampling model, the predicted mean AUC was 4.4 min x mg/ml (median 4.2, range 2.4-8.4, SD 1.2 min x mg/ml). Statistical analysis revealed that the model was slightly biased (MPE%, 6.5%), but imprecise (RMSE%, 20.6%) in our study population.Conclusion: Although easy and attractive to use, the Ghazal-Aswad formula is not precise enough to predict the carboplatin AUC, and needs to be evaluated prospectively in other patient populations. [ABSTRACT FROM AUTHOR]

Through extensive multisystem phenotyping, the central aim of Project PICMAN is to correlate metabolic flexibility to measures of cardiometabolic health, including myocardial diastolic dysfunction, coronary and cerebral atherosclerosis, body fat distribution and severity of non-alcoholic fatty liver disease. This cohort will form the basis of larger interventional trials targeting metabolic inflexibility in the prevention of cardiovascular disease. Participants aged 21-72 years with no prior manifest atherosclerotic cardiovascular disease (ASCVD) are being recruited from a preventive cardiology clinic and an existing cohort of non-alcoholic fatty liver disease (NAFLD) in an academic medical centre. A total of 120 patients will be recruited in the pilot phase of this study and followed up for 5 years. Those with 10-year ASCVD risk ≥ 5% as per the QRISK3 calculator are eligible. Those with established diabetes mellitus are excluded. Participants recruited undergo a detailed assessment of health behaviours and physical measurements. Participants also undergo a series of multimodality clinical phenotyping comprising cardiac tests, vascular assessments, metabolic tests, liver and neurovascular testing. Blood samples are also being collected and banked for plasma biomarkers, 'multi-omics analyses' and for generation of induced pluripotent stem cells (iPSC). Extensive evidence points to metabolic dysregulation as an early precursor of cardiovascular disease, particularly in Asia. We hypothesise that quantifiable metabolic inflexibility may be representative of an individual in his/her silent, but high-risk progression towards insulin resistance, diabetes and cardiovascular disease. The platform for interdisciplinary cardiovascular-metabolic-neurovascular diseases (PICMAN) is a pilot, prospective, multi-ethnic cohort study., (© 2023. The Author(s).)

Introduction: Bariatric surgery is considered an effective treatment for weight loss and for improving the metabolic profile of patients with obesity. Obesity-related comorbidities such as hyperlipidaemia and type 2 diabetes mellitus (DM) are significant cardiovascular risk factors. Additionally, prospective clinical trials have shown that statins increase the risk of development of DM, and many patients with obesity are on statins. We retrospectively examined the effect of bariatric surgery on lipid profile, DM control and weight loss at the five-year follow-up., Methods: In total, 104 patients undergoing bariatric surgery from 2008 to 2012 were retrospectively studied. 36 patients were on preoperative statins. Their lipid profile, DM control and weight loss were examined at the one-year and five-year follow-ups., Results: Both high-density lipoprotein and triglyceride levels showed significant improvement at the one-year and five-year follow-ups (p = 0.01). Total cholesterol showed significant improvement at the one-year follow-up (-0.30 mmol/dL, p = 0.0338); however, better control was not sustained at the five-year follow-up (-0.15 mmol/dL, p = 0.133). Low-density lipoprotein did not show any considerable improvement at the one- and five-year follow-ups (-0.27 mmol/dL, p = 0.150 and -0.24 mmol/dL, p = 0.138, respectively). A statistically significant improvement in DM control was observed in these patients and in those on preoperative statins. Weight loss was sustained at one and five years., Conclusion: Bariatric surgery does not confer a uniform improvement in lipid profile in the long term. It does, however, induce efficient weight loss and improvement in diabetic profile, even in patients on preoperative statins., (Copyright: © Singapore Medical Association.)

Contaminations of heavy metals such as lead (Pb) and cadmium (Cd) in medicinal plants (MPs) not only restrict their safe consumption due to health hazards but also lower their productivity. Biochar amendments in the soil are supposed to immobilize the toxic metals, improve the soil quality and agricultural productivity. However, the impact of biochar on growth attributes, metal accumulation, pharmacologically active compounds of MPs, and health risk is less explored. An experiment was performed on three medicinal plants (Bacopa monnieri (L.), Andrographis paniculata (Burmf.) Nees, and Withaniasomnifera (L.)) grown in a greenhouse in soil co-contaminated with Pb and Cd (at two concentrations) without and with biochar amendments (2 and 4% application rates). The fractionation of Pb and Cd, plant growth parameters, stress enzymes, photosynthetic capacity, pharmacologically active compounds, nutrient content, uptake and translocation of metals, antioxidant activities, and metabolite content were examined in the three MPs. The accumulation of Pb and Cd varied from 3.25-228 mg kg 1 and 1.29-20.2 mg kg -1 , respectively, in the three MPs, while it was reduced to 0.08-18 mg kg -1 and 0.03-6.05 mg kg -1 upon biochar treatments. Plants grown in Pb and Cd co-contaminated soil had reduced plant biomass (5-50% depending on the species) compared to control and a deleterious effect on photosynthetic attributes and protein content. However, biochar amendments significantly improved plant biomass (21-175%), as well as photosynthesis attributes, chlorophyll, and protein contents. Biochar amendments in Pb and Cd co-contaminated soil significantly reduced the health hazard quotient (HQ) estimated for the consumption of these medicinal herbs grown on metal-rich soil. An enhancement in secondary metabolite content and antioxidant properties was also observed upon biochar treatments. These multiple beneficial effects of biochar supplementation in Pb and Cd co-contaminated soil suggested that a biochar amendment is a sustainable approach for the safe cultivation of MPs. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

Background: Bone grafting is a dynamic phenomenon. It is a surgical procedure that replaces missing bone with material either from patient's own body, or, an artificial, synthetic or natural substitute. A successful bone graft when applied, heals, becomes incorporated, re-vascularises and eventually assumes the form desired., Aims and Objective: The main purpose of this present study was to radiologically assess and compare the regenerative potential of hydroxyapatite with Collagen (G-Graft) and hydroxyapatite (G-Bone) and to evaluate the clinical usefulness of these materials to enhance bone healing in third molar extraction sites through bone formation., Materials and Methods: The study was carried out in the Department of Oral & Maxillofacilal Surgery, patients were divided into three groups. The rationale for assigning the patients to the groups was strictly random: Group I - G-Graft (Hydroxyapatite with Collagen) was used as Bone graft material, Group II - Bone graft material used was G-Bone (Hydroxyapatite), Group III-control group (no grafts was used). Orthopentomogram(OPG) images were taken intra-operatively, just after extraction in the Group III (control), after extraction but before graft placement in Group I & II (study groups) and post-operatively at the end of first month and third month. Bone density of the post-extraction sockets was measured at four random areas through 'densitometric analysis' software in the OPG program (Kodak 8000C Digital Panoramic System, Eastman Kodak Company) and an average value was recorded at each review., Results: The percentage increase in bone density between 1(st) month & 3(rd) month was 7.55± 12.43 in Group I (G Graft), 4.41± 5.4859 in Group II (G Bone), while that Group III (control) was found to be -0.82 ± 3.96. The bone density increase was found to be statistically highly significant (p<0.01)) between all groups., Conclusion: The present study concluded that G-Graft has a definite regenerative potential and is better than G-bone and can be used in bony defects to enhance the bone healing without provoking any significant inflammatory process. The study also indicates that defects treated with G-Graft attain more density initially and that G-Graft enhances bone healing in early stage.

From previous studies, it is unclear how bimanual length discrimination differs from unimanual length discrimination. To investigate the difference, we designed an experiment with four conditions. In the first two conditions, unimanual and bimanual discrimination thresholds are determined. In the third and fourth conditions, length is explored with the two index fingers like in the bimanual condition, but the reference is either internal, by clasping the hands together, or external, by grasping handles connected to the table. We find that thresholds for the unimanual condition (7.0%) and the clasping condition (9.2%) are both lower than for the bimanual condition (16%) and the grasping handles condition (15%). We conclude that when discriminating length unimanually and bimanually while clasping the hands together, the internal reference within the hand can be used and that explains the lower discrimination thresholds.

We investigated if and how length and curvature information are integrated when an object is explored in one hand. Subjects were asked to explore four types of objects between thumb and index finger. Objects differed in either length, curvature, both length and curvature correlated as in a circle, or anti-correlated. We found that when both length and curvature are present, performance is significantly better than when only one of the two cues is available. Therefore, we conclude that there is integration of length and curvature. Moreover, if the two cues are correlated in a circular cross-section instead of in an anti-correlated way, performance is better than predicted by a combination of two independent cues. We conclude that integration of curvature and length is highly efficient when the cues in the object are combined as in a circle, which is the most common combination of curvature and length in daily life.

Importance: Cataracts are a main cause of low vision; with the growing elderly population, the incidence of cataracts is likely to increase. Investigators have previously hypothesized that statin antioxidant effects may slow the natural aging process of the lens., Objective: To compare the risks for development of cataracts between statin users and nonusers., Design: A propensity score-matched cohort analysis using retrospective data from October 1, 2003, to March 1, 2010. A propensity score-matched cohort of statin users and nonusers was created using 44 variables., Setting: Database of a military health care system., Participants: Based on medication fills during fiscal year 2005, patients were divided into 2 groups: (1) statin users (received at least a 90-day supply of statin) and (2) nonusers (never received a statin throughout the study). Among 46,249 patients meeting study criteria, we identified 13,626 statin users and 32,623 nonusers., Exposure: Use of statin therapy for more than 90 days., Main Outcomes and Measures: Primary analysis examined the risks for cataract in the propensity score-matched cohort. Secondary analyses examined the risks for cataract in patients with no comorbidities according to the Charlson Comorbidity Index (patients with no Charlson comorbidity). A sensitivity analysis was conducted to repeat the secondary analysis in patients taking statins for durations of 2, 4, and 6 years., Results: For our primary analysis, we matched 6972 pairs of statin users and nonusers. The risk for cataract was higher among statin users in comparison with nonusers in the propensity score-matched cohort (odds ratio, 1.09; 95% CI, 1.02-1.17). In secondary analyses, after adjusting for identified confounders, the incidence of cataract was higher in statin users in comparison with nonusers (odds ratio, 1.27; 95% CI, 1.15-1.40). Sensitivity analysis confirmed this relationship., Conclusions and Relevance: The risk for cataract is increased among statin users as compared with nonusers. The risk-benefit ratio of statin use, specifically for primary prevention, should be carefully weighed, and further studies are warranted.

For small stimuli, it has been shown that subjects are very accurate in distinguishing a cylinder with an elliptical cross section from one with a circular cross section. In such a task, both curvature and length are integrated effectively. Large cylinders are explored differently: either by one hand or by two hands sliding over the surface. However, the same cues are available. We investigated the integration of position and curvature in unimanual and bimanual explorations. In Experiment 1, curved surfaces were presented as part of a horizontal cylinder with a cross section that was either a horizontally or a vertically elongated ellipse. We found that discrimination thresholds for unimanual exploration were significantly larger than for bimanual exploration. In Experiment 2, we found that position discrimination thresholds were independent of the type of exploration (unimanual or bimanual) and surprisingly also independent of the reference length. In Experiment 3, we found that discrimination thresholds for the position of the midsagittal plane were on an average lower than the position discrimination thresholds found in Experiment 2. From these findings, we conclude that the lower thresholds in Experiment 1 for bimanual exploration compared to unimanual exploration are due to the integration of curvature, not position or uncertainty of the midsagittal plane in unimanual exploration.

Objectives: To compare topical interleukin 1 receptor antagonist (IL-1ra) to steroid treatment following photorefractive keratectomy (PRK) in rabbit eyes., Methods: Our study is a randomized, investigator-masked study that was approved by the Institutional Animal Care and Use Committee. Following standard PRK, 48 eyes of 24 rabbits were divided into 5 arms: 4 treatment arms and 1 control arm. The right eye of each rabbit served as the treatment eye, and the left eye served as a control. Eyes in treatment arms were randomized to receive either fluorometholone, 0.1%, 4 times a day (Falcon, Fort Worth, Texas), or 2.5, 1.25, or 0.25 mg of IL-1ra 4 times a day. Control eyes received only moxifloxacin hydrochloride, 0.5% (Vigamox; Alcon, Fort Worth, Texas), and a solution of polyethylene glycol 400, 0.4%, and propylene glycol, 0.3% (Systane; Alcon), 4 times a day. Primary outcome measures included weekly evaluation of subjective haze formation and time to corneal reepithelization with clinic examinations, objective haze formation using Pentacam technology (Oculus, Lynnwood, Washington), as well as histological examination for haze thickness 7 weeks after PRK., Results: There was no difference among treatment groups in time to reepithelization. The IL-1ra treatment groups showed a statistically significant reduction in haze formation (P < .001, determined by repeated-measures analysis of variance) on corneal evaluation using the Pentacam 3 weeks after PRK compared with the control group. This effect was comparable to that in the steroid treatment group. There was also a statistically significant effect of the treatment on subjective haze evaluation at weeks 4 and 5 (P < .05, determined by repeated-measures analysis of variance), but this effect lost statistical significance when the steroid group was excluded from the evaluation. In addition, there was no statistically significant difference in histologic evaluation of haze thickness among treatment groups (P = .997)., Conclusion: Further studies are needed to determine the efficacy and adverse effect profile of topical IL-1ra in human eyes., Clinical Relevance: IL-1ra therapy may be an alternative to steroid treatment following PRK.

Purpose: To report a case of a corneal ulcer caused by an unusual pathogen., Design: Case report., Methods: Clinical review describing initial presentation, course, and outcome of 1 patient with a corneal ulcer caused by Kingella denitrificans., Results: A 77-year-old man with a prior history of 4 penetrating keratoplasties in the right eye for herpes simplex virus keratitis presented with a 3-day history of a red painful right eye. On examination, he was found to have a corneal ulcer identified by culture as K. denitrificans., Conclusions: Although Kingella spp. is not a common ocular pathogen, it can infect the cornea, especially when the host immune defense is altered.

Introduction: The field of refractive surgery continues to evolve amid continued concerns as to which surgical technique minimizes the risk of inducing ectasia., Purpose: To compare clinical outcomes between PRK, LASEK and Epi-LASIK in moderately to highly myopic eyes (-4.00 D to -8.00 D)., Materials and Methods: A retrospective chart review of 100 PRK eyes, 100 LASEK eyes (with alcohol) and 97 Epi-LASIK eyes was performed. Post-operative pain, uncorrected visual acuity, and corneal haze data was recorded and analyzed at post-op days 1, 4 and 7 and at post-op months 1, 3, 6 and 12., Results: In all groups surgical corrections ranged from -4.00 D to -8.00 D. There was less pain associated with the epi-LASIK procedure especially early (post-op days 1 and 4). Visual recovery was superior within the PRK group during the first post-operative week but by post-op week 4 all three were equal. Haze scores were similar but a trend for less haze was demonstrated with epi-LASIK at 6 and 12 months., Conclusion: Epi-LASIK has a slight advantage over PRK and LASEK early on in the post-op course with regards to pain. Visual recovery is similar by 4 weeks and is better with PRK early. In addition, epi-LASIK trends toward less significant haze., (© Nepal Ophthalmic Society.)

A 33-year-old man who was 2 years post laser in situ keratomileusis was found to have corneal ectasia. He was intolerant of rigid gas-permeable contact lenses and eventually chose to have placement of intrastromal corneal ring segments (ICRS) (Intacs) in the right eye. Two ICRS were implanted without complication, and postoperative examination showed improved visual acuity and decreased corneal elevation on scanning-slit tomography imaging. However, over the following 2 months, he complained of persistent pain in the right eye. Confocal microscopy showed a corneal nerve touching the superonasal ICRS. The ICRS was removed, and shortly thereafter the patient's pain resolved., (Published by Elsevier Inc.)

The main purpose of this study was to investigate whether the coadministration of amifostine alters the pharmacokinetic behavior of paclitaxel. Eight patients were included in the study: six received paclitaxel in combination with epirubicin and cisplatin, and two received paclitaxel as a single agent. Doses of paclitaxel in these protocols were 135, 150, 175, and 200 mg/m(2) and two patients were treated at each dose level. Pharmacokinetic sampling for paclitaxel analysis was performed in each patient during two consecutive cycles, one with and one without amifostine (750 mg/m(2) as a 15-minute intravenous infusion 30 minutes before paclitaxel administration). At each dose level, the pharmacokinetic data of paclitaxel were compared per patient for a cycle without amifostine versus a cycle with amifostine. Amifostine did not seem to interact pharmacokinetically with paclitaxel, given either alone or in combination chemotherapy. This is in line with the clinical findings that amifostine has no negative effects on the antitumor activity of various antineoplastic agents. Also, amifostine may reduce toxic effects of combination chemotherapy regimens that include paclitaxel.

The purpose of our study was to investigate the pharmacokinetics of Cremophor EL following administration of escalating doses of Taxol (paclitaxel dissolved in Cremophor EL/ethanol) to non-small cell lung cancer (NSCLC) patients. Patients with NSCLC stage IIIb or IV without prior chemotherapy treatment were eligible for treatment with paclitaxel and carboplatin in a dose-finding phase I study. The starting dose of paclitaxel was 100 mg/m2 and doses were escalated with steps of 25 mg/m2, which is equal to a starting dose of Cremophor EL of 8.3 ml/m2 with dose increments of 2.1 ml/m2. Carboplatin dosages were 300, 350 or 400 mg/m2. Pharmacokinetic sampling was performed during the first and the second course, and the samples were analyzed using a validated high-performance liquid chromatographic assay. A total of 39 patients were included in this pharmacokinetic part of the study. The doses of paclitaxel were escalated up to 250 mg/m2 (20.8 ml/m2 Cremophor EL). Pharmacokinetic analyses revealed a low elimination-rate of Cremophor EL (CI=37.8-134 ml/h/m2; t 1/2=34.4-61.5 h) and a volume of distribution similar to the volume of the central blood compartment (Vss=4.96-7.85 l). In addition, a dose-independent clearance of Cremophor EL was found indicating linear kinetics. Dose adjustment using the body surface area, however, resulted in a non-linear increase in systemic exposure. The use of body surface area in calculations of Cremophor EL should therefore be re-evaluated.

Purpose: Carboplatin doses are often determined by using modified Calvert formulas. It has been observed that the area under the concentration versus time curve (AUC) for free carboplatin is lower than expected when modified formulas are used for carboplatin/paclitaxel chemotherapy combination regimens. By using limited-sampling models, the carboplatin AUC actually reached can easily be verified, and the dose adjusted accordingly., Methods: In this report, we describe the development and validation of a limited-sampling model for carboplatin from 77 pharmacokinetic curves, when carboplatin is used in combination with paclitaxel., Results: The following single-point model was selected as optimal: AUC carboplatin (min mg(-1) ml(-1)) = 418. c(2.5 h)(mg/ml) + 0.43 (min mg(-1) ml(-1)), where c(2.5 h) is the concentration (mg/ml) of carboplatin 2.5 h after the start of a 30-min infusion. This model proved to be unbiased (mean prediction error = 3.4 +/- 1.6%) and precise (root mean square error = 10.1 +/- 1.5%)., Conclusions: The proposed model can be very useful for ongoing and future carboplatin/paclitaxel studies aimed to optimise and individualize treatment.