Effect of maternal and infant covariates on sibship correlation in birth weight

Birth weight on 12,644 singleton infants from 6,196 sibships born in Maryland between 1980 and 1984 were used to estimate the effects of nine maternal and infant covariates on the sibship correlation in birth weight. Assuming a homogeneous correlation across all families, the estimated intraclass correlation was 0.4664 (+/- 0.0099). This high sibship correlation makes it possible to predict, with reasonable accuracy, the birth weight of a child given information on previous sibs, as well as covariates on the mother and/or infant pertinent to a given pregnancy. The reduction in variance associated with incorporating information on the nine covariates used here was approximately equal to that obtained by conditioning on a single previous sib. Testing for heterogeneity in correlation among different groups of families showed that a crude measure of parity (first live birth vs. other), time between births, mother's marital status, and maternal age at the birth of the last child significantly influenced the sibship correlation in birth weight.     

Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian 'Special Access Scheme' experience

Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m² or carboplatin AUC = 5 and pemetrexed 500 mg/m² every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively. Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.     

Toll-like receptor signaling inhibits structural development of the distal fetal mouse lung.

We tested the hypothesis that innate immune signaling in utero could disrupt the structural development of the fetal lung, contributing to the pathogenesis of bronchopulmonary dysplasia. Injection of Escherichia coli lipopolysaccharide (LPS) into the amniotic fluid of E15 BALB/cJ mice increased the luminal volume density of fetal mouse lungs at embryonic day (E) 17 and E18. LPS also increased luminal volume and decreased distal lung branching in fetal mouse lung explants. This effect required NF-kappaB activation and functional Toll-Like Receptor 4. Airway branching may require fibronectin-dependent epithelial-mesenchymal interactions, representing a potential target for innate immune signaling. Anti-fibronectin antibodies and LPS both blocked distal lung branching. By immunofluorescence, fibronectin localized to the clefts between newly formed airways but was restricted to peripheral mesenchymal cells in LPS-exposed explants. These data suggest that LPS may alter the expression pattern of mesenchymal fibronectin, potentially disrupting epithelial-mesenchymal interactions and inhibiting distal airway branching and alveolarization. This mechanism may link innate immune signaling with defects in structural development of the fetal lung.     

Selective photothermolysis: contribution to the treatment of flat angiomas (port wine stains) by laser

Since 1962, lasers have been used in dermatology and have become the first choice in the treatment of superficial, vascular ectasia. Lasers are unique sources of light; they are coherent, monochromatic, collimated and intense. By careful selection of wavelength, pulse duration, and intensity, it is often possible to selectively confine a laser effect to a specific histologic structure in tissue, depending upon the tissue properties. The ideal treatment of Port Wine Stains (PWS) should irreversibly damage the ectatic vessels but minimize heating of the epidermis and superficial dermis. A theory, called selective photothermolysis, predicts the optimal combination of laser parameters of achieving this ideal treatment of PWS to be a wavelength of 577 nm, a pulse duration of 0.35-10 msec, and an energy per surface area of about 7-8 J/cm2. Laser wavelength: The wavelength of 577 nm is preferred because it: maximizes the selective absorption by hemoglobin, minimizes absorption by epidermal melanin, provides sufficient depth of penetration in the blood to coagulate 0.1 mm vessels allows penetration of light into dermis up to 1 mm. Laser pulse duration: A pulse-width in the range of 0.35-10 msec allows the temperature elevation to be uniform inside the vessel and to be confined to the vessel area. Shorter pulses superheat the red blood cells causing explosive boiling and hemorrhage. Longer pulses allow heat to diffuse away from vessels, requiring greater energies per pulse to achieve vessel damage. An increased energy per pulse increases the risk of excessive damage to surrounding tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Automatic algorithm for correcting motion artifacts in time-resolved two-dimensional magnetic resonance angiography using convex projections.

Time-resolved contrast enhanced magnetic resonance angiography (MRA) may suffer from involuntary patient motion. It is noted that while MR signal change associated with motion is large in magnitude and has smooth phase variation in k-phase, signal change associated with vascular enhancement is small in magnitude and has rapid phase variation in k-space. Based upon this observation, a novel projection onto convex sets (POCS) algorithm is developed as an automatic iterative method to remove motion artifacts. The presented POCS algorithm consists of high-pass phase filtering and convex projections in both k-space and image space. Without input of detailed motion knowledge, motion effects are filtered out, while vasculature information is preserved. The proposed method can be effective for a large class of nonrigid motions, including through-plane motion. The algorithm is stable and converges quickly, usually within five iterations. A double-blind evaluation on a set of clinical MRA cases shows that a completely unsupervised version of the algorithm produces significantly better rank scores (P=0.038) when compared to angiograms produced manually by an experienced radiologist.     

Beta carotene uptake into atherosclerotic plaque: Enhanced staining and preferential ablation with the pulsed dye laser

The yellow color of atherosclerotic plaque is due to the presence of carotenoids, which absorb light between 430–530 nm and account for the preferential ablation of plaque by the pulsed dye laser operating at 480 nm. This study was designed to examine tissue uptake of β-carotene and the effect of uptake on arterial plaque ablation. Forty-two atherosclerotic NZW rabbits were given intravenous β-carotene at a dose of 40 mg/kg, twice weekly and killed between 1 hour and 28 days after the initial injection. β-carotene was not detected in control specimens but was significantly greater in plaque than in normal wall at all time points following β-carotene injection (P < 0.04 Mann Whitney U test). The ablation threshold was significantly lower in β-carotene treated plaque than in untreated plaque or normal arterial wall (P < 0.01, Fisher's exact test). In this model β-carotene is preferentially taken up into arterial plaque, resulting in increased absorption of laser radiation at 480 nm and enhanced tissue ablation. © 1993 Wiley-Liss, Inc.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

High-Temperature Short-Time Heat Inactivation of HIV and Other Viruses in Human Blood Plasma

An ultra-short-time heating system was used to process blood plasma spiked with various viruses (HIV, vesicular stomatitis virus, encephalomyocarditis virus). Virus reduction and recovery of plasma proteins were measured at various temperatures from 65 to 85 degrees C. Processing at 77 degrees C and 0.006 s resulted in a high level of virus kill, including greater than or equal to 4.4 log10 HIV, while maintaining protein structure and activity essentially intact.