Serum glomerular permeability activity in patients with podocin mutations (NPHS2) and steroid-resistant nephrotic syndrome

A plasma factor displaying permeability activity in vitro and possibly determining proteinuria has been hypothesized in idiopathic focal segmental glomerulosclerosis (FSGS). In vitro permeability activity (P(alb)) was determined in sera of five patients with autosomal recessive steroid-resistant nephrotic syndrome (NPHS2), an inherited condition indistinguishable from idiopathic FSGS on clinical grounds, but in which proteinuria is determined by homozygous mutations of podocin, a key component of the glomerular podocyte. All patients had presented intractable proteinuria with nephrotic syndrome; four developed renal failure and received a renal allograft. For comparison, sera from 31 children with nephrotic syndrome were tested. Pretransplant P(alb) was high in all cases (mean 0.81 +/- 0.06), equivalent to levels observed in idiopathic FSGS. Overall, P(alb) did not correlate with proteinuria. The posttransplant outcome was complicated in two patients by recurrence of proteinuria after 10 and 300 d, respectively, that responded to plasmapheresis plus cyclophosphamide. P(alb) levels were high at the time of the recurrence episodes and steadily decreased after plasmapheresis, to reach normal levels in the absence of proteinuria after the seventh cycle. In an attempt to explain high P(alb) in these patients, putative inhibitors of the permeability activity were studied. Coincubation of serum with homologous nephrotic urine reduced P(alb) to 0, whereas normal urine did not determine any change, which suggests loss of inhibitory substances in nephrotic urine. The urinary levels of the serum P(alb) inhibitors apo J and apo E were negligible in all cases, thus suggesting that other urinary inhibitors were responsible for the neutralizing effect. These data indicate that P(alb) is high in NPHS2, probably resulting from loss of inhibitors in urine. Lack of correlation of P(alb) with proteinuria suggests a selective loss of inhibitors. As in idiopathic FSGS, proteinuria may also recur after renal transplantation in NPHS2 patients, and post-transplant proteinuria is associated with high P(alb). The relationship between elevated P(alb) and proteinuria in NPHS2 remains to be determined.     

Discrepancies in frozen section mucosal margin tissue in laryngeal squamous cell carcinoma

BACKGROUND: Head and neck surgeons commonly request frozen sections. Practice patterns vary from laboratory to laboratory on how the tissue is used in performing the frozen section. Some pathologists wish to see all the material submitted by consuming it completely during frozen section, whereas others reserve some for permanent section. We wished to determine whether knowledge of margin status was initially inaccurate because of reserving tissue for permanent section. METHODS: Sixty-five laryngectomies (total and partial) with margin assessment enhanced by frozen section evaluation were studied. Forty-five laryngectomy specimens, generating 249 frozen sections in which a permanent section was prepared from tissue remaining from frozen section examination, were studied. RESULTS: Five of the 249 frozen sections contained a discrepancy between the frozen section and permanent section because of insufficient leveling of the frozen section block. These five discrepancies were called negative on frozen section, but permanent section revealed dysplasia (two cases of mild dysplasia, one case with moderate dysplasia, and one case with severe dysplasia) or carcinoma in situ (one case). Twenty laryngectomies in which the frozen section tissue was consumed at the time of frozen section generated 103 frozen sections. In eight of the frozen sections involving six cases, the diagnostic tissue was not present on one or two of the frozen section levels examined. CONCLUSIONS: We conclude that in examining margins for laryngeal squamous cell carcinoma the frozen section tissue should be completely sampled by examining several levels at the time of frozen section. This requires consuming or exhausting the frozen section tissue rather than reserving any remaining frozen tissue for a paraffin-embedded permanent section.     

Changing incidence of out-of-hospital ventricular fibrillation, 1980-2000

Context  Recent reports from 2 European cities and an earlier observation from Seattle, Wash, suggest that the number of patients treated for out-of-hospital ventricular fibrillation (VF) has declined. Objective  To analyze the incidence of cardiac arrest and to examine relationships among incidence, sex, race, age, and first identified cardiac rhythm in Seattle. Design, Setting, and Patients  Population-based study of all cardiac arrest cases with presumed cardiac etiology who received advanced life support from Seattle Fire Department emergency medical services during specified periods between 1979 and 2000. United States Census data for Seattle in 1980, 1990, and 2000 were used to determine incidence rates for treated cardiac arrest with adjustments for age and sex. Main Outcome Measures  Changes in incidence of cardiac arrest and initial recorded cardiac rhythm. Results  The adjusted annual incidence of cardiac arrest with VF as the first identified rhythm decreased by about 56% from 1980 to 2000 (from 0.85 to 0.38 per 1000; relative risk [RR], 0.44; 95% confidence interval [CI], 0.37-0.53). Similar reductions occurred in blacks (54%; RR, 0.45; 95% CI, 0.26-0.79) and whites (53%; RR, 0.47; 95% CI, 0.38-0.58) and was most evident in men (57%; RR, 0.43; 95% CI, 0.35-0.53), in whom the baseline incidence was relatively high. When all treated arrests with presumed cardiac etiology were considered, that incidence decreased by 43% (RR, 0.58; 95% CI, 0.49-0.67) in men but negligibly in women, for whom a relatively low incidence of VF also declined but was offset by more cases with asystole or pulseless electrical activity. Conclusion  We observed a major decline in the incidence of out-of-hospital VF and in all cases of treated cardiac arrest presumably due to heart disease in Seattle. These changes likely reflect the national decline in coronary heart disease mortality.      

Improving quality of care for acute myocardial infarction: The Guidelines Applied in Practice (GAP) Initiative

Context  Quality of care of patients with acute myocardial infarction (AMI) has received intense attention. However, it is unknown if a structured initiative for improving care of patients with AMI can be effectively implemented at a wide variety of hospitals. Objective  To measure the effects of a quality improvement project on adherence to evidence-based therapies for patients with AMI. Design and Setting  The Guidelines Applied in Practice (GAP) quality improvement project, which consisted of baseline measurement, implementation of improvement strategies, and remeasurement, in 10 acute-care hospitals in southeast Michigan. Patients  A random sample of Medicare and non-Medicare patients at baseline (July 1998–June 1999; n = 735) and following intervention (September 1–December 15, 2000; n = 914) admitted at the 10 study centers for treatment of confirmed AMI. A random sample of Medicare patients at baseline (January–December 1998; n = 513) and at remeasurement (March–August 2001; n = 388) admitted to 11 hospitals that volunteered, but were not selected, served as a control group. Intervention  The GAP project consisted of a kickoff presentation; creation of customized, guideline-oriented tools designed to facilitate adherence to key quality indicators; identification and assignment of local physician and nurse opinion leaders; grand rounds site visits; and premeasurement and postmeasurement of quality indicators. Main Outcome Measures  Differences in adherence to quality indicators (use of aspirin, -blockers, and angiotensin-converting enzyme [ACE] inhibitors at discharge; time to reperfusion; smoking cessation and diet counseling; and cholesterol assessment and treatment) in ideal patients, compared between baseline and postintervention samples and among Medicare patients in GAP hospitals and the control group. Results  Increases in adherence to key treatments were seen in the administration of aspirin (81% vs 87%; P = .02) and -blockers (65% vs 74%; P = .04) on admission and use of aspirin (84% vs 92%; P = .002) and smoking cessation counseling (53% vs 65%; P = .02) at discharge. For most of the other indicators, nonsignificant but favorable trends toward improvement in adherence to treatment goals were observed. Compared with the control group, Medicare patients in GAP hospitals showed a significant increase in the use of aspirin at discharge (5% vs 10%; P<.001). Use of aspirin on admission, ACE inhibitors at discharge, and documentation of smoking cessation also showed a trend for greater improvement among GAP hospitals compared with control hospitals, although none of these were statistically significant. Evidence of tool use noted during chart review was associated with a very high level of adherence to most quality indicators. Conclusions  Implementation of guideline-based tools for AMI may facilitate quality improvement among a variety of institutions, patients, and caregivers. This initial project provides a foundation for future initiatives aimed at quality improvement.      

Collecting direct non-health care and time cost data: application to screening and diagnosis of cervical cancer.

BACKGROUND: Data on direct non-health care and time costs are rarely collected, though the incorporation of such data is essential for performing cost-effectiveness analyses according to established guidelines. OBJECTIVES: To explore the challenges involved in collecting and analyzing these data from patients enrolled in a clinical trial. METHODS: Through the use of a pilot study, the authors designed a questionnaire to collect these costs. They used this questionnaire in a clinical trial conducted at a comprehensive cancer center and a public community hospital. Patients in the trial were undergoing screening or diagnostic procedures through a clinical protocol designed to measure the effectiveness of fluorescence and reflectance spectroscopy for detecting cervical precancers. Direct non-health care costs were adjusted to 2003 constant dollars. RESULTS: The authors successfully collected direct non-health care and time cost data, thus demonstrating the feasibility of acquiring such data. Compared to patients receiving diagnostic services for cervical cancer, those receiving screening services for the same condition in both settings incurred lower direct non-health care costs and time costs, as defined in the questionnaire. Compared to patients receiving either service at the comprehensive cancer center, those seeking either service at the public community hospital incurred lower direct non-health care costs and time costs. When outliers were removed, total direct non-health care costs and time costs substantially decreased for diagnostic patients in the comprehensive cancer center; total direct non-health care costs and time costs for other subgroups remained essentially unchanged. CONCLUSIONS: Direct non-health care and time cost data can be collected within a large-scale clinical trial. The setting (community v. specialty hospital) and population (patients receiving screening v. diagnostic examination) makes a difference regarding the cost totals. The order of magnitude of the final result depends on the context in which the non-health care and time cost data will be used.     

Italian multicentric pilot study on MBL2 genetic polymorphisms in HIV positive pregnant women and their children.

OBJECTIVE: We investigated genetic polymorphisms of MBL2 gene, in a cohort of 90 Italian HIV-1 pregnant seropositive women and their children in order to understand whether the MBL2 genotype of HIV-1 positive mothers might be related to their ability to transmit the virus to their children. MATERIALS AND METHODS: DNA was extracted from Iso Code Stix cards, and MBL2 genotyping was performed by Melting Temperature Assay. RESULTS: The frequency of the MBL2 0/0 homozygotes was higher in HIV-1 positive mothers than in healthy controls, the MBL2 0/0 genotype was more frequent in children born from HIV positive mothers than healthy subjects. CONCLUSIONS: We have confirmed the association of polymorphisms involving a gene of the innate immunity with an increased risk of being infected by HIV. These polymorphisms were also evidenced in children born from HIV+ mothers, but the risk of infection was strongly reduced by cesarean delivery and by antiretroviral treatment.     

Critical appraisal of Perez et al: Jugular venous oxygen saturation or arteriovenous difference of lactate content and outcome in children with severe traumatic brain injury.

OBJECTIVE: To review the findings and discuss the implications of jugular venous bulb oxygenation monitoring in children with severe traumatic brain injury. DESIGN: A critical appraisal of Perez et al, Jugular venous oxygen saturation or arteriovenous difference of lactate content and outcome in children with severe traumatic brain injury. FINDINGS: Two episodes of jugular venous bulb desaturation and abnormal values of arteriovenous difference in lactate content are associated with poor neurologic outcome in children with severe traumatic brain injury-risk ratio 6.6 (95% confidence interval, 1.5-29.7) and risk ratio 17.6 (95% confidence interval, 2.5-122.5), respectively. This confirms the findings of previously reported adult studies. CONCLUSIONS: This study is the first to demonstrate that jugular venous monitoring may aid in predicting the neurologic outcome of children with severe traumatic brain injury. More studies need to be performed (particularly on safety) before adopting jugular venous bulb oxygenation monitoring as a prediction tool or, ultimately, as a therapeutic intervention to help manage and improve outcome for children with severe traumatic brain injury.     

Photodynamic therapy with verteporfin for retinal angiomatous proliferation

Purpose The aim of this study was to evaluate the results of photodynamic therapy (PDT), using verteporfin, for subfoveal neovascular age-related macular degeneration (ARMD) with retinal angiomatous proliferation (RAP) with pigment epithelial detachment (PED) and/or choroidal neovascularization (CNV).Methods In this non-comparative, consecutive, interventional, case series, the data on 21 eyes (19 with stage 2 and two with stage 3 RAP) of 20 patients were reviewed. Serous PED occupied more than 50% of the lesion in 19 eyes. PDT was performed as per TAP protocol. Biomicroscopy and fluorescein and indocyanine-green angiography were performed to evaluate anatomical results and need for retreatment. Changes from baseline in best-corrected visual acuity (BCVA), and complications, were assessed.Results A mean of 3.5±0.9 treatments was performed. After 13.7±2.2 months, mean BCVA decreased from 20/80 to 20/174 (P=0.0063). In six eyes (28.6%) BCVA remained stable, whereas in 15 eyes (71.5%) it decreased. Occlusion of RAP and flattening of PED was observed in three (14.2%) eyes, conversion to disciform lesion in one (4.7%), and persistence of PED in 11 eyes (52.3%). One eye (4.7%) evolved to haemorrhagic PED, and one (4.7%) toward stage 3 RAP. A tear in the retinal pigment epithelium (RPE) was observed in four eyes (19%). Eleven (52.3%) showed progression of leakage, six moderate leakage (28.6%), and three (14.2%) absence of leakage.Conclusions Timely PDT with verteporfin in the early stages in eyes with smaller lesions has the potential for a beneficial effect on vision, whereas it might worsen the natural course of larger lesions, with most eyes undergoing enlargement, disciform transformation or RPE tear.Presented in part as a paper at the American Academy of Ophthalmology Annual Meeting, Anaheim, California, 15–18 November 2003The authors have no financial interest in this study     

Effect of montelukast on exhaled NO in asthmatic children exposed to relevant allergens

The level of exhaled nitric oxide (FENO) is increased in house dust mite (HDM)-sensitized asthmatic children after exposure to HDM antigen, and inhaled steroids can prevent this increase. The aim of this study was to evaluate whether montelukast could prevent an increase in FENO levels in allergic asthmatic children after a brief period of exposure to relevant allergens. Sixteen children were evaluated at the residential house 'Istituto Pio XII' (Misurina, Bellunio, Italy) in the Italian Alps, a dust mite-free environment. FENO levels were evaluated before ( t ₀) and immediately after ( t ₁) the children were exposed to HDM allergens for 2 weeks in their homes at sea level. No significant difference in FENO was observed in the fluticasone-treated group of children after 2 weeks at sea level. In the group treated with montelukast, an increase in FENO was observed between t ₀ and t ₁, which failed to reach statistical significance. These preliminary data suggest that oral montelukast could be effective in preventing the relapse in airway inflammation in allergic asthmatic children who are occasionally exposed to relevant allergens for a short period of time.