Intraocular pressure control and complications with two-stage insertion of the Baerveldt implant

PURPOSE: To evaluate intraocular pressure (IOP) control and the prevalence of complications associated with the two-stage insertion of the Baerveldt implant. DESIGN: Retrospective, noncomparative, interventional case series. METHODS: We reviewed the medical records of all patients who underwent the two-stage Baerveldt implantation for advanced glaucoma between January 1995 and November 1998 at the Doheny Eye Institute, Los Angeles, California. All eyes with a minimum of 6 months of follow-up were included in the study. Eyes that failed before 6 months after stage II were also included in the study. MAIN OUTCOME MEASURES: The criterion for surgical success was postoperative IOP of 6 mmHg or more and 21 mmHg or less on two or more consecutive measurements with or without the use of glaucoma medications and without loss of light perception or further surgical intervention to lower IOP. RESULTS: Nineteen eyes from 19 patients were included. Median postoperative follow-up was 17 months (range, 3-56 months). The cumulative probability of success was 89% at both 12 and 24 months. The median preoperative IOP of 21 mmHg (range, 12-33 mmHg) was reduced to a median postoperative IOP of 12 mmHg (range, 1-17 mmHg; P < 0.0001). The median number of glaucoma medications before surgery was three and after surgery was one (P < 0.0001). Visual acuity remained the same or improved in 13 eyes (68%). One eye experienced hypotony (5%), and in two eyes (11%) suprachoroidal hemorrhages developed. CONCLUSIONS: The two-stage insertion of the Baerveldt implant effectively reduced IOP, produced few complications, and preserved visual acuity in more than two thirds of eyes with advanced glaucomatous damage.     

Frontal cortex atrophy predicts cognitive impairment in multiple sclerosis

The association between regional measures of cortical atrophy and neuropsychological (NP) dysfunction was studied in 35 multiple sclerosis (MS) patients. Patients underwent neurological examination, MRI, and NP testing. Blind quantitative MRI analysis yielded total T(2) lesion area (TLA) and third ventricle width (3VW). Cortical atrophy, rated by blind visual inspection, was more extensive in superior frontal and parietal cortices than in other regions. No MRI measures were correlated with depression scores. TLA and 3VW were significantly correlated with each NP test. Cortical atrophy measures for bilateral superior frontal cortex were retained in regression models predicting impairments in verbal learning, spatial learning, attention, and conceptual reasoning. The authors conclude that cerebral atrophy predicts NP impairment while accounting for the influence of TLA or 3VW. Regions of cortex most susceptible to atrophic and cognitive changes in MS are the right and left superior frontal lobes.     

Effect of the insulin mimetic L-783,281 on intracellular Ca2+ and insulin secretion from pancreatic beta-cells

L-783,281, an antidiabetic fungal metabolite that has previously been shown to activate insulin signaling in CHO cells, was tested for its effect on intracellular Ca(2+) ([Ca(2+)](i)) and insulin secretion in single mouse pancreatic beta-cells. Application of 10 micromol/l L-783,281 for 40 s to isolated beta-cells in the presence of 3 mmol/l glucose increased [Ca(2+)](i) to 178 +/- 10% of basal levels (n = 18) as measured by fluo-4 fluorescence. L-767,827, an inactive structural analog of the insulin mimetic, had no effect on beta-cell [Ca(2+)](i). The L-783,281-evoked [Ca(2+)](i) increase was reduced by 82 +/- 4% (n = 6, P < 0.001) in cells incubated with 1 micromol/l of the SERCA (sarco/endoplasmic reticulum calcium ATPase) pump inhibitor thapsigargin and reduced by 33 +/- 6% (n = 6, P < 0.05) in cells incubated with 20 micromol/l of the L-type Ca(2+)-channel blocker nifedipine. L-783,281-stimulated [Ca(2+)](i) increases were reduced to 31 +/- 3% (n = 9, P < 0.05) and 48 +/- 10% (n = 6, P < 0.05) of control values by the phosphatidylinositol 3-kinase (PI3-K) inhibitors LY294002 (25 micromol/l) and wortmannin (100 nmol/l), respectively. In beta-cells from IRS-1-/- mice, 10 micromol/l L-783,281 had no significant effect on [Ca(2+)](i) (n = 5). L-783,281 also resulted in insulin secretion at single beta-cells. Application of 10 micromol/l L-783,281 for 40 s resulted in 12.2 +/- 2.1 (n = 14) exocytotic events as measured by amperometry, whereas the inactive structural analog had no stimulatory effect on secretion. Virtually no secretion was evoked by L-783,281 in IRS-1-/- beta-cells. LY294002 (25 micromol/l) significantly reduced the effect of the insulin mimetic on beta-cell exocytosis. It is concluded that L-783,281 evokes [Ca(2+)](i) increases and exocytosis in beta-cells via an IRS-1/PI3-K-dependent pathway and that the [Ca(2+)](i) increase involves release of Ca(2+) from intracellular stores.     

Anatomic Location of the Tongue Base Neurovascular Bundle

Knowledge of the location of the hypoglossal/lingual artery neurovascular bundle (HLNVB) is essential in performing tongue base resections for neoplasm and for obstructive sleep apnea. Transoral and transcervical resections of the tongue base may be performed with greater exposure and certainty when the relationship of the HLNVB to local landmarks is understood; knowledge of the HLNVB allows resection of a larger amount of contralateral tongue base during partial glossectomy without violating the contralateral remnant tongue's blood supply. Ten cadaver heads were dissected to determine the position of the HLNVB with respect to soft tissue and bony landmarks at the tongue base. Our results indicate the position of the tongue base HLNVB is significantly inferior and lateral, that is, 2.7 cm inferior and 1.6 cm lateral to the foramen cecum, 0.9 cm superior to the hyoid bone, and 2.2 cm medial to the mandible. This inferolateral location allows the potential for aggressive tongue base resection without neurovascular compromise.     

Diffuse magnetic resonance imaging white-matter changes in a 15-year-old boy with mitochondrial encephalomyopathy

We report a 15-year-old boy who presented with recurrent headaches associated with numbness, confusion, and speech difficulty. Brain magnetic resonance imaging (MRI) revealed diffuse bilateral white-matter hyperintensity on fluid-attenuated inversion-recovery and T2-weighted images in the internal capsule, periventricular and subcortical white matter, base of the pons, and middle cerebellar peduncles. Lesions were isointense on T1-weighted images and nonenhancing. Muscle biopsy showed changes consistent with a mitochondrial myopathy. Mitochondrial respiratory chain enzyme activity analysis revealed a significant reduction in complex II activity. Genetic testing was negative. We conclude that mitochondrial encephalomyopathy may present with unusual diffuse supratentorial and infratentorial white-matter changes on MRI.     

Epidemiology of chronic suppurative otitis media and deafness in a rural area and developing an intervention strategy

Of 613 children evaluated in a village in Haryana 94 (15.3%) were observed to have chronic suppurative otitis media (CSOM). Fifty eight (61.7%) children had hearing impairment. CSOM contributed to 71.6% of the hearing impaired (58/81). On analysis of association of CSOM with literacy and socio-economic status of mothers, and age, sex, and upper respiratory tract infections (URI) in children positive correlation was observed only with URIs (P<0.001). Literacy and socio-economic status of the mothers did not correlate significantly with knowledge about treatment seeking, and ear cleaning practices, probably due to the narrow range of incomes and literacy levels. An intervention program consisting of play, demonstrations, health charts and slogans, and aural cleaning and antibiotic drops was introduced.     

Integrative genomics analysis reveals silencing of beta-adrenergic signaling by polycomb in prostate cancer

The Polycomb group (PcG) protein EZH2 possesses oncogenic properties for which the underlying mechanism is unclear. We integrated in vitro cell line, in vivo tumor profiling, and genome-wide location data to nominate key targets of EZH2. One of the candidates identified was ADRB2 (Adrenergic Receptor, Beta-2), a critical mediator of beta-adrenergic signaling. EZH2 is recruited to the ADRB2 promoter and represses ADRB2 expression. ADRB2 inhibition confers cell invasion and transforms benign prostate epithelial cells, whereas ADRB2 overexpression counteracts EZH2-mediated oncogenesis. ADRB2 is underexpressed in metastatic prostate cancer, and clinically localized tumors that express lower levels of ADRB2 exhibit a poor prognosis. Taken together, we demonstrate the power of integrating multiple diverse genomic data to decipher targets of disease-related genes.     

A cost-effectiveness analysis of first-line controller therapies for persistent asthma

BACKGROUND: Asthma is one of the most common chronic diseases in the US, and its prevalence continues to increase. Despite the availability of effective asthma controller medications, many patients with asthma are still not meeting therapeutic goals because of poor disease management. The high disease prevalence combined with the high costs associated with the poor management of asthma, make patients with asthma a costly group to treat for managed care organisations (MCOs) and this motivates decision makers in MCOs to consider both the clinical and economic value of asthma therapies. OBJECTIVE: To compare the cost effectiveness of first-line controller asthma therapies in patients with mild-to-moderate persistent asthma from an MCO payer perspective. METHODS: A decision-analysis model was developed to evaluate the cost effectiveness of fluticasone propionate and salmeterol administered in a single inhaler (salmeterol/fluticasone propionate 50/100microg), compared with fluticasone propionate inhaled corticosteroids (FPIC), non-fluticasone propionate inhaled corticosteroids (nFPIC) and leukotriene modifiers. The model estimated costs ($US, year 2005 values) and health outcomes over a 1-year period. Costs and outcomes data were obtained from published clinical trials and observational studies, and model assumptions on the relationship between adherence and effectiveness were evaluated by a panel of experts. Effectiveness measures included symptom-free days and rescue medication-free days. The cost effectiveness of first-line asthma therapies was compared using a step-wise approach, with FPIC as the reference case. Both one-way and probabilistic sensitivity analyses were performed to assess the robustness of results over a range of assumptions. RESULTS: The step-wise comparison found that the additional costs for achieving an incremental effectiveness unit (incremental cost-effectiveness ratio) using single-inhaler salmeterol/fluticasone propionate compared with FPIC was $US9.55 per symptom-free day and $US8.93 per rescue medication-free day. Sensitivity analyses indicated that the model was robust to changes in base-case assumptions. A probabilistic sensitivity analysis showed that, corresponding to a benchmark value of $US14.8 per symptom-free day, the probabilities that single-inhaler salmeterol/fluticasone propionate, n-FPIC and leukotriene modifiers were more cost effective than FPIC were 98%, 30.7% and 2.1%, respectively. CONCLUSION: Based on our decision analysis, the additional costs for achieving incremental effectiveness with single-inhaler salmeterol/fluticasone propionate treatment compared with FPIC and nFPIC may be lower than the commonly accepted benchmark value for cost effectiveness, based on published estimates of the utility losses associated with asthma symptoms. Single-inhaler salmeterol/fluticasone propionate may also be more cost effective than leukotriene modifiers.