Correlating Papanicolaou Smear, Colposcopic Impression, and Biopsy: Results from the Women's Interagency HIV Study

OBJECTIVE: To determine associations among cervical cytology, colposcopy, and biopsy in HIV-seropositive women. MATERIALS AND METHODS: HIV-seropositive women and uninfected comparison women in a multicenter prospective cohort study underwent colposcopy for protocol indications. Women were eligible if they had a cervix, satisfactory cytology, and colposcopy between October 1994 and September 1999. Cytology, colposcopic impression, and biopsy were compared using equivalent categorizations. Kappa statistics with bootstrap sampling assessed strength of associations. RESULTS: Colposcopy was performed in 978/1370 HIV-seropositive women and in 154/224 seronegative women. Biopsies were performed on 603 (44%) seropositive women at least once during 1015 colposcopy visits and on 82 (37%) seronegative women at 116 visits. The positive predictive value of cytology was 72% for seropositive women and 60% for seronegative women. The positive predictive value of colposcopy was 71% for seropositive women and 55% for seronegative women. CONCLUSION: The correlation between either cervical cytology or colposcopic impression and colposcopic biopsy was poor.     

Simplified model of laser Doppler signals during reactive hyperaemia

Laser Doppler flowmetry (LDF) is a non-invasive method to measure tissue blood flow. During reactive hyperaemia, the LDF signal increases to a peak and then returns to a resting value. A simplified model is developed to explain these variations. The emphasis is on simulating the effects occurring rather than on trying to mimic the anatomical structure of the microcirculation. A single blood vessel is therefore analysed. The increasing value of blood velocity is studied, and vasodilatation as well as vasoconstriction are taken into account. The model parameters are calculated using wavelets. For a 2-min occlusion on a healthy subject, the radius of the vessel is initially 15 μm, increasing to 24.6 μm at the peak, reached 14 s after the release of the occlusion. The model shows that the high value of the LDF signal during the initial phase of reactive hyperaemia is produced by an increasing number of erythrocytes in a cross-section, due to vasodilatation rather than an increase in moving blood cell velocities. Moreover, the rapidity of the vasodilatation and vasoconstriction effects determine the rapidity of the signal variations. The paper aims to give a basic solution to develop a numerical model.     

Consequences of interaction of a lipophilic endotoxin antagonist with plasma lipoproteins

E5531, a novel synthetic lipid A analogue, antagonizes the toxic effects of lipopolysaccharide, making it a potential intravenously administered therapeutic agent for the treatment of sepsis. This report describes the distribution of E5531 in human blood and its activity when it is associated with different lipoprotein subclasses. After in vitro incubation of [(14)C]E5531 with blood, the great majority (>92%) of material was found in the plasma fraction. Analysis by size-exclusion and affinity chromatographies and density gradient centrifugation indicates that [(14)C]E5531 binds to lipoproteins, primarily high-density lipoproteins (HDLs), with distribution into low-density lipoproteins (LDLs) and very low density lipoproteins (VLDLs) being dependent on the plasma LDL or VLDL cholesterol concentration. Similar results were also seen in a limited study of [(14)C]E5531 administration to human volunteers. The potency of E5531 in freshly drawn human blood directly correlates to increasing LDL cholesterol levels. Finally, preincubation of E5531 with plasma or purified lipoproteins indicated that binding to HDL resulted in a time-dependent loss of drug activity. This loss in activity was not observed with drug binding to LDLs or to VLDLs or chylomicrons. Taken together, these results indicate that E5531 binds to plasma lipoproteins, making its long-term antagonistic potency dependent on the plasma lipoprotein composition.     

The Pediatric Cardiomyopathy Registry: 1995–2007

Cardiomyopathy is a serious disorder of the heart muscle and, although rare, it is potentially devastating in children. Funded by the National Heart Lung and Blood Institute since 1994, the Pediatric Cardiomyopathy Registry (PCMR) was designed to describe the epidemiology and clinical course of selected CMs in patients 18 years old or younger and to promote the development of etiology-specific prevention and treatment strategies. Currently, data from more than 3000 children with cardiomyopathy have been entered in the PCMR database with annual follow-up continuing until death, heart transplant, or loss-to-follow up. Using PCMR data, the incidence of cardiomyopathy in two large regions of the United States is estimated to be 1.13 cases per 100,000 children. Only 1/3 of children had a known etiology at the time of cardiomyopathy diagnosis. Diagnosis was associated with certain patient characteristics, family history, echocardiographic findings, laboratory testing, and biopsy. Greater incidence was found in boys and infants (< 1 yr) for both dilated and hypertrophic cardiomyopathy (DCM, HCM) and black race for only DCM. In DCM, prognosis is worse in older children (> 1 yr), heart failure (HF) at diagnosis or idiopathic etiology. For HCM, worse prognosis is associated with inborn errors of metabolism or combination of HCM and another cardiomyopathy functional type. The best outcomes were observed in children presenting at age > 1 yr with idiopathic HCM. PCMR data have enabled analysis of patients with cardiomyopathy and muscular dystrophy, as well as Noonan Syndrome. Currently, collaborations with the Pediatric Heart Transplant Study group and a newly established Pediatric Cardiomyopathy Biologic Specimen Repository at Texas Children's Hospital will continue to yield important results. The PCMR is the largest and most complete multi-center prospective data resource regarding the etiology, clinical course and outcomes for children with cardiomyopathy.     

Potential cost-effectiveness of vaccination for rotavirus gastroenteritis in eight Latin American and Caribbean countries.

OBJECTIVES: To estimate the costs, benefits and cost-effectiveness of vaccination for rotavirus gastroenteritis in eight Latin American and Caribbean countries: Argentina, Brazil, Chile, the Dominican Republic, Honduras, Mexico, Panama, and Venezuela. METHODS: An economic model was constructed to estimate the cost-effectiveness of vaccination from the health care system perspective, using national administrative and published epidemiological evidence, country-specific cost estimates, and vaccine efficacy data. The model was applied to the first five years of life for the 2003 birth cohort in each country. The main health outcome was the disability-adjusted life year (DALY), and the main summary measure was the incremental cost per DALY averted. A 3% discount rate was used for all predicted costs and benefits. Sensitivity analyses evaluated the impact of uncertainty regarding key variables on cost-effectiveness estimates. RESULTS: According to the estimates obtained with the economic model, vaccination would prevent more than 65% of the medical visits, deaths, and treatment costs associated with rotavirus gastroenteritis in the eight countries analyzed here. At a cost of US$ 24 per course (for a two-dose vaccine), the incremental cost-effectiveness ratio ranged from 269 US dollars/DALY in Honduras to 10,656 US dollars/DALY in Chile. Cost-effectiveness ratios were sensitive to assumptions about vaccine price, mortality, and vaccine efficacy. CONCLUSIONS: Vaccination would effectively reduce the disease burden and health care costs of rotavirus gastroenteritis in the Latin American and Caribbean countries analyzed here. From the health care system perspective, universal vaccination of infants is predicted to be cost-effective, based on current standards.     

Use of recombinant activated factor VII in intractable bleeding during pediatric neurosurgical procedures.

OBJECTIVE: To report the use of recombinant activated factor VII (NovoSeven; Novo Nordisk A/S, Bagsvaerd, Denmark) in children undergoing major neurosurgical procedures and experiencing massive uncontrolled hemorrhagic shock. DESIGN: Retrospective review of patients and analysis of clinical and biological effects of an intravenous administration of recombinant activated factor VII. SETTING: Neurosurgical anesthesia and critical care unit of a pediatric university hospital. PATIENTS/SUBJECTS: Four children, <12-kg body weight, experiencing life-threatening perioperative hemorrhage required conventional treatment (massive red blood cells, fresh frozen plasma, platelet transfusion, and surgical hemostatic maneuvers) that failed to obtain definite hemostasis. INTERVENTIONS: Intravenous administration of recombinant activated factor VII (100 microg/kg). RESULTS: Intravenous administration resulted in a significant decrease in blood loss within minutes (preventing further need of transfusion), normalization of biological hemostasis markers, and improved surgical hemostasis. No side effects of recombinant activated factor VII were noted, and all patients, except one, had a good recovery. CONCLUSIONS: These four patients support the use of recombinant activated factor VII as a useful adjunct to control massive life-threatening bleeding during pediatric neurosurgical procedures when other means failed. However, the data are still limited in children, and more extensive research is needed to define the indications of recombinant activated factor VII in massive surgical hemorrhage in low-weight children.     

Evaluation of Left Ventricular Diastolic Performance Using Automated Border Detection

Acoustic quantification (AQ) is a noninvasive technique which provides online left ventricular (LV) area/volume waveforms. The filling portion of the AQ waveform can be used to assess LV diastolic properties. Analysis of signal-averaged AQ curves enhances the waveforms and allows reliable, quantitative, and automated analysis. From signal-averaged AQ LV waveforms, the phases of diastole can be easily detected and several parameters of diastolic performance calculated. Analysis of signal-averaged LV waveforms is complementary to that of LV AQ analysis. AQ has been used to identify diastolic dysfunction in patients with LV hypertrophy and systemic hypertension. Normal values of these parameters are age dependent and reference values will soon be available.     

Randomized trial of diethylstilbestrol vs. tamoxifen in postmenopausal women with metastatic breast cancer. An updated analysis

One hundred fiftyone postmenopausal women with progressive metastatic breast cancer and no prior hormonal therapy were treated with either diethylstilbestrol (DES) or tamoxifen (TAM). One hundred fortythree eligible patients were followed until death or for a minimum of 14.1 years on the DES arm or 16.7 years on the TAM arm. The overall objective response was 42% for DES and 33% for TAM (p=0.31) and the median duration of response was 11.8 months for DES and 9.9 months for TAM (p=0.38). Duration of response and progressionfree survival were not found to be significantly different between DES and TAM (p=0.32 and 0.65, respectively). The median survival was 3.0 years for DES vs. 2.4 years for TAM. The 5year survival was 35% for the DES arm and 16% for the TAM arm. Survival was significantly better for women on DES than for women on TAM (adjusted p=0.039). Review of records did not show any difference in pattern of treatment failure or subsequent treatments in the DES and TAM arms.Treatment with DES was more commonly associated with toxicity such as nausea, edema, vaginal bleeding, and cardiac problems, whereas hot flashes were commonly seen with TAM therapy.The initial treatment with DES is associated with increased survival. The basis of this survival advantage is not known. TAM still is the preferred agent in the treatment of metastatic breast cancer, but this trial underscores the fact that estrogens have activity and remain in the armamentarium for treatment of selected patients with metastatic breast cancer.     

Thirty years of universal home dialysis in Christchurch

AIM: To review 30 years of universal home dialysis in a single dialysis unit. METHOD: Analysis for patients using home dialysis since 1969 of information from hospital visits, clinical case notes and demographic and survival data from the Australia and New Zealand Dialysis and Transplant Registry. RESULTS: Since 1969 treatment options at the Christchurch Nephrology Unit for patients with end-stage renal disease have been home haemodialysis (HD), renal transplantation and, since 1979, continuous ambulatory peritoneal dialysis (CAPD). No long-term, hospital-based treatment has been offered. During this time 493 patients, aged 3-82 years, began treatment. The mean training time for home HD was 79 days (range 23-268) and for home CAPD 7 days (range 1-35). The mean HD treatment time was 7 hours x 3 per week (range 10-36 hours/week). Between 1980 and 1995, less than 5% of patients took antihypertensive drugs and 73% of those aged 18-65 years were in full or part-time employment. The mean age of patients commencing treatment increased from 41.8 years in the 1970s to 50.1 years in the 1990s. The median patient survival from 1970-1997 was 7.75 years on home HD and 2.1 years on home CAPD. Median survival on dialysis fell in the 1990's as more diabetics and older patients with comorbidity started treatment. CONCLUSIONS: Home HD allows good rehabilitation, long treatment times and good blood pressure control which may all contribute to the superior survival of home versus hospital HD. CAPD survival in Christchurch was worse than HD, but this is probably due to patient selection. A policy of universal home dialysis is still workable provided there are sufficient resources for training and support of patients in the community.