Contrast-based sensorless adaptive optics for retinal imaging

Conventional adaptive optics ophthalmoscopes use wavefront sensing methods to characterize ocular aberrations for real-time correction. However, there are important situations in which the wavefront sensing step is susceptible to difficulties that affect the accuracy of the correction. To circumvent these, wavefront sensorless adaptive optics (or non-wavefront sensing AO; NS-AO) imaging has recently been developed and has been applied to point-scanning based retinal imaging modalities. In this study we show, for the first time, contrast-based NS-AO ophthalmoscopy for full-frame in vivo imaging of human and animal eyes. We suggest a robust image quality metric that could be used for any imaging modality, and test its performance against other metrics using (physical) model eyes.OCIS codes: (010.1080) Active or adaptive optics, (170.3880) Medical and biological imaging, (170.4460) Ophthalmic optics and devices, (330.4875) Optics of physiological systems     

Adaptive optics imaging of the retinal microvasculature

The eye has long been recognised as the window to pathological processes occurring in the brain and other organs. By imaging the vasculature of the retina we have improved the scientific understanding and clinical best practice for a diverse range of conditions, ranging from diabetes, to stroke, to dementia. Mounting evidence suggests that damage to the smallest and most delicate vessels in the body, the capillaries, is the first sign in many vasculopathies. These are the most critical vessels involved in the exchange of metabolites with tissue. Accurate assessment of retinal capillary structure and function would therefore be of great benefit across a broad range of disciplines in medical science; however, their small size does not make this an easy task. This has led to the development of high-resolution adaptive optics imaging methods to non-invasively explore retinal microvascular networks in living human eyes. This review describes the present state of the art in the field, the scientific breakthroughs that have been made possible in the understanding of vessel structure and function in health and disease, and future directions for this emerging technology.     

Phase I study of temozolomide and irinotecan for recurrent malignant gliomas in patients receiving enzyme-inducing antiepileptic drugs: a north american brain tumor consortium study.

PURPOSE: To determine the maximum tolerated dose of irinotecan when administrated with temozolomide every 28 days, in patients with recurrent malignant glioma who were also receiving CYP450 enzyme-inducing antiepileptic drugs (EIAED), and to characterize the pharmacokinetics of irinotecan and its metabolites. The study was also intended to assess whether temozolomide affects the conversion of irinotecan to SN-38. DESIGN: Patients with recurrent malignant glioma received a fixed dose of temozolomide (150 mg/m(2)) daily for 5 days from days 1 to 5 every 28 days, and an i.v. infusion of irinotecan on days 1 and 15 of each cycle. The starting dose of irinotecan was 350 mg/m(2), which was escalated to 550 mg/m(2) in 50-mg/m(2) increments. The plasma pharmacokinetics of irinotecan and its active metabolite, SN-38, were determined during the infusion of irinotecan on cycle 1, day 1. RESULTS: Thirty-three patients were enrolled into the study and treated. Thirty-one patients were evaluable for both tumor response and toxicity and two patients were evaluable for toxicity only. Common toxicities included neutropenia and thrombocytopenia, nausea, vomiting, and diarrhea. Dose-limiting toxicities were grade 3 diarrhea and nausea/vomiting. The maximum tolerated dose for irinotecan was determined to be 500 mg/m(2). CONCLUSIONS: The recommended phase II dose of irinotecan in combination with temozolomide for patients receiving EIAEDs is 500 mg/m(2), administrated every 15 days on a 28-day schedule. This study also confirmed that concomitant administration of EIAEDs increases irinotecan clearance and influences SN-38 disposition. No pharmacokinetic interaction was observed between temozolomide and irinotecan.     

High carbohydrate diet in the treatment of diabetes mellitus

Summary Restriction of carbohydrate in the diet of diabetics is widely advocated and practised in the Western Countries, but poses a special problem in the treatment of vegetarian diabetic patients in India, since cereals like wheat and rice constitute the major bulk of their diet. Drastic changes in the diet may be needed to curtail carbohydrate intake. 25 adult-onset diabetic patients were therefore allowed to eat their customary diet, and the control of their diabetes was studied. Restrictions were made only in the total caloric intake, where needed, by curtailing fats. The average carbohydrate consumption was 342 g, constituting 67% of the average total caloric intake. Prompt and adequate clinical and biochemical control of diabetes could be achieved by a moderate dose of oral hypoglycaemie agents or insulin, and maintained during their followup period of 6 months to 8 years without any difficulty despite their high carbohydrate intake. Avantages of such a diet are enumerated.

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Kohlenhydratreiche Diät in der Behandlung des Diabetes mellitus

Zusammenfassung Die Einschränkung der Kohlenhydrate in der Diät des Diabetikers wird in den Ländern des Westens viel empfohlen und geübt; sie bietet aber bei der Behandlung von diabetischen Vegetariern in Indien spezielle Probleme, da bei ihnen Getreideprodukte wie Weizen und Reis den überwiegenden Teil der Diät ausmachen. Eine Einschränkung der Kohlenhydratzufuhr würde daher bei diesen Patienten auf eine ausgesprochen drastische Umstellung der Diät hinauslaufen. Bei 25 Diabetikern vom Erwachsenen-Typ wurde daher die Einstellung des Diabetes kontrolliert, während sie ihre gewohnte Kost beibehielten. Soweit eine Kalorieneinschränkung erforderlich war, erfolgte sie durch Verringerung der Fettzufuhr. Der durchschnittliche Kohlenhydratverbrauch belief sich dabei auf 342 g, d.h. 70% der mittleren Kalorienaufnahme/Tag. Trotz der hohen KH-Zufuhr ließ sich bei diesen Patienten ohne Schwierigkeiten mit mittleren Dosen von oralen Antidiabetika oder Insulin eine gute Diabetes-Einstellung während der Untersuchungsperiode, die sieh über 1/2–8 Jahre ausdehnte, erzielen. Die Vorteile einer derartigen Diät werden aufgeführt.

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Alimentation riche en hydrates de carbone au cours du traitement du diabète sucré

Résumé La restriction des hydrates de carbone dans le régime des diabétiques est largement recommandée et pratiquée dans les pays occidentaux, mais pose un problème particulier dans le traitement des diabétiques végétariens en Inde, car les céréales telles que le blé et le riz constituent la majeure partie de leur régime. Des changements énergiques dans le régime peuvent être nécessaires pour diminuer la prise d'hydrates de carbone. 25 diabétiques adultes ont donc été autorisés à suivre leur régime habituel, et l'équilibre de leur diabète a été étudié. Les restrictions étaient faites seulement dans l'apport calorique total, quand cela était nécessaire, par réduction des matières grasses. La consommation moyenne d'hytrates de carbone était de 342 g, constituant 67% de l'apport calorique total moyen. Un bon contrôle clinique et biochimique du diabète pouvait être réalisé par l'administrationd'une dose modérée d'agents hypoglycémiants oraux ou d'insuline, et maintenu sans difficulté pendant la période d'observation allant de 6 mois à 8 ans, malgré l'apport élevé d'hydrates de carbone. Les avantages d'un tel régime sont énumérés.

     

A clinico-pathological study of postcoital bleeding

Methods. To undertake a clinical study of postcoital bleeding (PCB) in a district general hospital we retrospectively reviewed the records of 248 patients referred to the gynaecology department over a 5-year period. Results. 63% were in the 21–40-year age group and 80% were multiparous. Seventy per cent were referred to the gynaecology out patients' clinic and 28% to the colposcopy clinic. Associated symptoms included menstrual abnormalities (39%) and dyspareunia (13%). Twenty per cent had benign polyps, including endometrial polyps and 25% had cervical ectropion. Cervical intraepithelial neoplasia was detected in 6.8% of cases. There was no case of invasive cancer of the lower genital tract. Conclusions. This is the first report of associated endometrial polyps contributing to PCB. We conclude that CIN may not always be asymptomatic and the incidence of cervical or endometrial cancer is low in women with PCB.     

Low-Frequency Drug Resistance in HIV-Infected Ugandans on Antiretroviral Treatment Is Associated with Regimen Failure

Most patients failing antiretroviral treatment in Uganda continue to fail their treatment regimen even if a dominant drug-resistant HIV-1 genotype is not detected. In a recent retrospective study, we observed that approximately 30% of HIV-infected individuals in the Joint Clinical Research Centre (Kampala, Uganda) experienced virologic failure with a susceptible HIV-1 genotype based on standard Sanger sequencing. Selection of minority drug-resistant HIV-1 variants (not detectable by Sanger sequencing) under antiretroviral therapy pressure can lead to a shift in the viral quasispecies distribution, becoming dominant members of the virus population and eventually causing treatment failure. Here, we used a novel HIV-1 genotyping assay based on deep sequencing (DeepGen) to quantify low-level drug-resistant HIV-1 variants in 33 patients failing a first-line antiretroviral treatment regimen in the absence of drug-resistant mutations, as screened by standard population-based Sanger sequencing. Using this sensitive assay, we observed that 64% (21/33) of these individuals had low-frequency (or minority) drug-resistant variants in the intrapatient HIV-1 population, which correlated with treatment failure. Moreover, the presence of these minority HIV-1 variants was associated with higher intrapatient HIV-1 diversity, suggesting a dynamic selection or fading of drug-resistant HIV-1 variants from the viral quasispecies in the presence or absence of drug pressure, respectively. This study identified low-frequency HIV drug resistance mutations by deep sequencing in Ugandan patients failing antiretroviral treatment but lacking dominant drug resistance mutations as determined by Sanger sequencing methods. We showed that these low-abundance drug-resistant viruses could have significant consequences for clinical outcomes, especially if treatment is not modified based on a susceptible HIV-1 genotype by Sanger sequencing. Therefore, we propose to make clinical decisions using more sensitive methods to detect minority HIV-1 variants.