Individuals with and without normal tension glaucoma exhibit comparable performance on tests of cognitive function

AIM: To evaluate aspects of cognition impacted by individuals with and without normal tension glaucoma. METHODS: Fifty normal tension glaucoma (NTG) and 50 control patients ≥50y of age were recruited from the UCSF Department of Ophthalmology. Demographic data and glaucoma parameters were extracted from electronic medical records for both groups. Tests of executive function [Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER)] and learning and memory [California Verbal Learning Test–Second Edition (CVLT-II)] were administered to both NTG and controls. Race, handedness, best-corrected visual acuity, maximum intraocular pressure, optic nerve cup-to-disc ratio, visual field and optic nerve optical coherence tomography parameters, and a measure of general health (Charlson Comorbidity Index) were compared between NTG and controls as well as within NTG subgroups. Multivariate linear regression was used to compare group performances on the EXAMINER battery and CVLT-II while controlling for age, sex, and years of education. RESULTS: NTG and controls were comparable with respect to age, sex, race, education, handedness, and the Charlson Comorbidity Index (P>0.05 for all). Performance on the EXAMINER composite score and the CVLT-II did not differ between NTG and controls (P>0.05 for both). CONCLUSION: This is the first prospective study in which the cognitive function of subject with NTG were evaluated using a comprehensive, computerized neurocognitive battery. Subjects with NTG do not perform worse than unaffected controls on tests of executive function, learning, and memory. Results do not support the hypothesis that individuals with NTG are at higher risk for cognitive dysfunction and/or dementia.     

Sodium chloride or plasmalyte-148 for patients presenting to emergency departments with diabetic ketoacidosis: A nested cohort study within a multicentre,cluster, crossover,randomised, controlled trial

Objective

To test the hypothesis that fluid resuscitation in the ED with plasmalyte-148 (PL) compared with 0.9% sodium chloride (SC) would result in a lower proportion of patients with diabetic ketoacidosis (DKA) requiring intensive care unit (ICU) admission.

Methods

We performed a prespecified nested cohort study at two hospitals within a cluster, crossover, open label, randomised, controlled trial comparing the effects of PL versus SC as fluid therapy for patients who presented to the ED with DKA. All patients presenting within a fixed recruitment period were included. The primary outcome was the proportion of patients admitted to ICU.

Results

Eighty-four patients were enrolled (SC n = 38, PL n = 46). The SC group had a lower median pH on admission (SC: 7.09 [interquartile range (IQR) 7.01–7.21], PL: 7.17 [IQR 6.99–7.26]). The median volume of intravenous fluids administered in ED was 2150 mL (IQR 2000–3200 mL; SC) and 2200 mL (IQR 2000–3450; PL); respectively. A higher proportion of patients in the SC group, 19 (50%), was admitted to ICU compared with PL group, 18 (39.1%); however, after adjustment for pH at presentation and diabetes type in a multivariable logistic regression model, the PL group did not have a significantly different rate of ICU admission compared with the SC group (odds ratio for ICU admission 0.73, 95% confidence interval 0.13–3.97, P = 0.71).

Conclusion

Patients with DKA treated with PL compared with SC in the EDs had similar rates of requiring ICU admission.     

High resolution imaging of normal and osteoarthritic cartilage with optical coherence tomography

OBJECTIVE: We describe optical coherence tomography (OCT), a high resolution micron scale imaging technology, for assessment of osteoarthritic articular cartilage microstructure. OCT is analogous to ultrasound, measuring the intensity of backreflected infrared light rather than acoustical waves. METHODS: OCT imaging was performed on over 100 sites on 20 normal and osteoarthritic cartilage specimens in vitro. RESULTS: Microstructures that were identified included fibrillations, fibrosis, cartilage thickness, and new bone growth at resolutions between 5 and 15 microm. In addition, the polarization sensitivity of imaging suggested a diagnostic role of polarization spectroscopy. CONCLUSION: OCT represents an attractive new technology for intraarticular imaging due to its high resolution (greater than any available clinical technology), ability to be integrated into small arthroscopes, compact portable design, and relatively low cost.     

Proliferation and cytogenetic analysis of hairy cell leukemia upon stimulation via the CD40 antigen

Using the CD40 system, in vitro proliferation of hairy cell leukemia (HCL) was examined in 43 patients. In this culture system, cells were stimulated by interleukin-4 (IL-4) and anti-CD40 monoclonal antibodies (MoAbs) that were added in soluble form or were cross-linked via their Fc part using Fc gamma RII-transfected mouse fibroblast cells. Proliferation was induced and confirmed by 3H-thymidine incorporation in 14 cases and by the presence of metaphases in 42 cases. 3H-thymidine incorporation showed a heterogeneous pattern: cross-linking of anti- CD40 gave the highest proliferation in 8 cases; in 11 cases, stimulation with anti-CD40 MoAbs alone, without cross-linking also resulted in proliferation; the addition of IL-4 further enhanced 3H- thymidine incorporation in 5 cases, but suppressed this phenomenon in 5 other cases. The CD40 system proved to be very effective in obtaining cytogenetic data. With a success rate of 42 of 43 patients tested, we found clonal abnormalities in 8 cases (19%) and nonclonal abnormalities with involvement of one or two abnormal metaphases in another 7 cases. The chromosomes most frequently involved in the abnormal karyotypes, both structurally and numerically, were chromosomes 5, 7, and 14. By fluorescence-activated cell-sorting analysis of the cultured cells, and by immunophenotypic analysis of metaphase spreads, T-cell growth could be excluded and the HCL-lineage confirmed. Stimulation via the CD40 antigen is an excellent tool for growing hairy cell leukemia cells.     

Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia

A phase I clinical trial was initiated to treat patients with stage IV B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65) antigen found on normal T lymphocytes, malignant T lymphocytes, and B- derived CLL cells. All of the patients had a histologically confirmed diagnosis of advanced B-derived CLL and were refractory to standard therapy, and more than 50% of their leukemia cells reacted with the T101 antibody in vitro. The patients received T101 antibody two times per week, over two to 50 hours by intravenous administration in 100 mL of normal saline containing 5% human albumin. Twelve patients were treated with a fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140 mg of antibody. It was demonstrated that patients given two-hour infusions of 50 mg developed pulmonary toxicity, with shortness of breath and chest tightness. This toxicity was eliminated when infusions of 50 or 100 mg of T101 were prolonged to 50 hours. All dose levels caused a rapid but transient decrease in circulating leukemia cell counts. In vivo binding to circulating and bone marrow leukemia cells was demonstrated at all dose levels with increased binding at higher dosages. Antimurine antibody responses were not demonstrated in any patients at any time during treatment. Circulating free murine antibody was demonstrated in the serum of only the two patients treated with 100 mg of antibody as a 50-hour infusion and the patient treated with 140 mg of antibody over 30 hours. Antigenic modulation was demonstrated in patients treated at all dose levels but was particularly apparent in patients treated with prolonged infusions of 50 and 100 mg of antibody. We were also able to demonstrate antigenic modulation in lymph node cells, which strongly suggests in vivo labeling of these cells. Overall, T101 antibody alone appears to have a very limited therapeutic value for patients with CLL. The observations of in vivo labeling of tumor cells, antigenic modulation, antibody pharmacokinetics, toxicity, and antimurine antibody formation may be used in the future for more effective therapy when drugs or toxins are conjugated to the antibody.     

Comparison of Five Chromogenic Media for Recovery of Vancomycin-Resistant Enterococci from Fecal Samples

Five chromogenic agars, evaluated using 400 stool specimens, were found to be superior in sensitivity (range, 89.9 to 93.9%) to bile esculin azide agar with vancomycin (BEAV) agar (84.8%) for detecting vancomycin-resistant enterococci (VRE), and the results were available 24 to 48 h sooner. The time to detection, need for supplemental testing, color distinction, and breakthrough of non-VRE organisms vary among the chromogenic media tested and may factor into the decision to use a particular medium.     

State of the art and recommendationsKangaroo mother care: application in a high‐tech environment

Since Kangaroo Mother Care (KMC) was developed in Colombia in the 1970s, two trends in clinical application emerged. In low income settings, the original KMC model is implemented. This consists of continuous (24 h/day, 7 days/week) and prolonged mother/parent–infant skin‐to‐skin contact; early discharge with the infant in the kangaroo position; (ideally) exclusive breastfeeding; and, adequate follow‐up. In affluent settings, intermittent KMC with sessions of one or a few hours skin‐to‐skin contact for a limited period is common. As a result of the increasing evidence of the benefits of KMC for both infants and families in all intensive care settings, KMC in a high‐tech environment was chosen as the topic for the first European Conference on KMC, and the clinical implementation of the KMC model in all types of settings was discussed at the 7th International Workshop on KMC. Kangaroo Mother Care protocols in high‐tech Neonatal Intensive Care Units (NICU) should specify criteria for initiation, kangaroo position, transfer to/from KMC, transport in kangaroo position, kangaroo nutrition, parents’ role, modification of the NICU environment, performance of care in KMC, and KMC in case of infant instability. Conclusion: Implementation of the original KMC method, with continuous skin‐to‐skin contact whenever possible, is recommended for application in high‐tech environments, although scientific evaluation should continue.     

Synthesis and protein kinase inhibitory activity of balanol analogues with modified benzophenone subunits

A series of analogues of the protein kinase C (PKC) inhibitory natural product balanol which bear modified benzophenone subunits are described. The analogues were designed with the goal of uncovering structure-activity features that could be used in the development of PKC inhibitors with a reduced polar character compared to balanol itself. The results of these studies suggest that most of the benzophenone features found in the natural product are important for obtaining potent PKC inhibitory compounds. However, several modifications were found to lead to selective inhibitors of the related enzyme protein kinase A (PKA), and several specific modifications to the polar structural elements of the benzophenone were found to provide potent PKC inhibitors. In particular, it was found that replacement of the benzophenone carboxylate with bioisosteric equivalents could lead to potent analogues. Further, a tolerance for lipophilic substituents on the terminal benzophenone ring was uncovered. These results are discussed in light of recently available structural information for PKA.