Congenital acinar dysplasia: a lethal entity

Congenital acinar dysplasia is a lethal, developmental lung malformation resulting in neonatal respiratory insufficiency. This entity is characterized by pulmonary hypoplasia and arrest in the pseudoglandular stage of development, resulting in the absence of functional gas exchange. The etiology is unknown, but a relationship with the disruption of the TBX4-FGF10 pathway has been described. There are no definitive antenatal diagnostic tests. It is a diagnosis of exclusion from other diffuse embryologic lung abnormalities with identical clinical presentations that are, however, histopathologically distinct

Limited B-mode venous imaging versus complete color-flow duplex venous scanning for detection of proximal deep venous thrombosis

AbstractPurpose: The purpose of this study was to compare the accuracy of a limited B-mode compression technique (BMCT) with a complete color-flow duplex venous examination (CDVE) for the detection of proximal deep vein thrombosis (DVT).Methods: We prospectively studied 72 patients (20 men and 52 women) for DVT. Two technologists blinded to each other performed either BMCT or CDVE independently. The BMCT is an abbreviated technique compressing two sites per limb. One site was the saphenofemoral junction including the superficial femoral and deep femoral vein confluence; the other was the saphenopopliteal junction including tibial vein confluence. Total limbs studied were 144. CDVE was considered the gold standard for purposes of sensitivity, specificity, and accuracy.Results: The technical failure rate of BMCT was three of 144. In all technically satisfactory examinations, the BMCT result was positive in 15 of 141 limbs, and the CDVE result was positive in 13. Sensitivity of BMCT was 100%, specificity was 98%, and overall accuracy was 99%. There were two false-positive results with BMCT; both were cases of popliteal veins deep to the artery leading to difficulty in compression. The BMCT was able to detect chronic thrombus, floating thrombus, and small thrombus behind femoral vein valve cusps.Conclusion: These data suggest that BMCT is a rapid, acceptable, alternative technique for detecting proximal DVT. In cases of equivocal or positive findings, the spectral and color-flow Doppler examination should be used to confirm the results. (J VASC SURG 1995;22:553-7.

Fiscal Year 1998

The Waste Information Requirements Document describes the activities of the Tank Waste Remediation System (TWRS) Characterization Project that provide characterization information on Hanford Site waste tanks. The characterization information is required to perform operations and meet the commitments of TWRS end users. These commitments are derived from the Hanford Federal Facility Agreement and Consent Order, also known as the Tri-Party Agreement; the Recommendation 93-5 Implementation Plan to the Defense Nuclear Facilities Safety Board (DNFSB); and other directives as listed in Section 4.0. This Waste Information Requirement Document applies to Fiscal Years 1997 and 1998 activities. Its contents are based on the best information available in August 1997. The format and content are based on the directions of DOE-RL (Sieracki, 1997) and Fluor Daniel Hanford Incorporated (Umek, 1997). Activities, such as the revision of the Tank Characterization Technical Sampling Basis (Brown et al. 1997), the revision of the data quality objectives (DQOs), issue closures, discussions with Ecology, and management decisions may cause subsequent updates to the Waste Information Requirements Document

Reduced Androgen Receptor Expression Accelerates the Onset of ERBB2 Induced Breast Tumors in Female Mice

Androgen receptor (AR) is commonly expressed in both the epithelium of normal mammary glands and in breast cancers. AR expression in breast cancers is independent of estrogen receptor alpha (ERα) status and is frequently associated with overexpression of the ERBB2 oncogene. AR signaling effects on breast cancer progression may depend on ERα and ERBB2 status. Up to 30% of human breast cancers are driven by overactive ERBB2 signaling and it is not clear whether AR expression affects any steps of tumor progression in this cohort of patients. To test this, we generated mammary specific Ar depleted mice (MARKO) by combining the floxed allele of Ar with the MMTV-cre transgene on an MMTV-NeuNT background and compared them to littermate MMTV-NeuNT, Arfl/+ control females. Heterozygous MARKO females displayed reduced levels of AR in mammary glands with mosaic AR expression in ductal epithelium. The loss of AR dramatically accelerated the onset of MMTV-NeuNT tumors in female MARKO mice. In this report we show that accelerated MMTV-NeuNT-dependent tumorigenesis is due specifically to the loss of AR, as hormonal levels, estrogen and progesterone receptors expression, and MMTV-NeuNT expression were similar between MARKO and control groups. MMTV-NeuNT induced tumors in both cohorts displayed distinct loss of AR in addition to ERα, PR, and the pioneer factor FOXA1. Erbb3 mRNA levels were significantly elevated in tumors in comparison to normal mammary glands. Thus the loss of AR in mouse mammary epithelium accelerates malignant transformation rather than the rate of tumorigenesis

Diabetes mellitus type 2 is associated with increased tumor expression of programmed death-ligand 1 (PD-L1) in surgically resected non-small cell lung cancer - A matched case-control study

OBJECTIVES: Programmed death-ligand 1 (PD-L1) expression is a biomarker for cancer immunotherapy. Diabetes mellitus type-2 is a comorbid disease associated with adverse outcomes in Non-Small Cell Lung Cancer (NSCLC). We aimed to investigate the differences in PD-L1 expression in diabetics. METHODS: A matched case-control cohort of surgically-resected NSCLC was assembled from an early multicenter study (PMID: 19152440). PD-L1 immunohistochemistry (Clone 22C3) was graded by a tumor positive score (TPS) system (TPS0: no staining; TPS1: \u3c 1%; TPS2: 1-49%; TPS3: \u3e /=50%). Variables showing significance at univariate survival analysis were fit in a Cox regression survival model. RESULTS: Diabetics (n=40) and nondiabetics (n=39) showed no differences in age, gender, cancer stage, and follow-up. NSCLCs were more likely PD-L1 positive in diabetics but with tumor positivity \u3c 50% (TPS0: 7.5 vs. 20.5%, TPS1: 35 vs. 25.6%, TPS2: 45 vs.23.1%, TPS3: 12.5 vs. 30.8%, respectively; P \u3c 0.05). In diabetics, squamous cell carcinomas (SCC) and adenocarcinomas were mainly TPS2 (65% vs. 20%) and TPS1 (50% vs. 26%), respectively. Peritumoral inflammation correlated with TPS (r=0.228), a relationship accentuated in diabetics (r=0.377, P \u3c 0.05) but diminished and non-significant in nondiabetics (r=0.136, P \u3e /=0.05). This association was stronger in SCC (r=0.424). Diabetes was associated with increased tumor recurrence (HR: 3.08; 95%CI: 1.027-9.23). CONCLUSION: Diabetes is associated with an increase in peritumoral inflammation, PD-L1 positivity, and recurrence in NSCLC, more pronounced in SCC, suggesting the possibility of metabolic reprogramming and upregulation of PD-L1 by inducible pathways. reserved

A k2A-positive Klebsiella pneumoniae causes liver and brain abscess in a Saint Kitt's man

Klebsiella pneumoniae isolated in community-acquired pneumonia is increasingly found in primary pyogenic liver abscesses. The presence of magA in K. pneumoniae has been implicated in hypermucoviscosity and virulence of liver abscess isolates. The K2 serotype has also been strongly associated with hypervirulence. We report the isolation of non-magA, K2 K. pneumoniae strain from a liver abscess of a Saint Kitt's man who survived the invasive syndrome

Hanford waste tanks - light at the end of the tunnel

The U.S. Department of Energy (DOE) faced several problems in its Hanford Site tank farms in the early nineties. It had 177 waste tanks, ranging in size from 55,000 to 1,100,000 gallons, which contained more than 55 million gallons of liquid and solid high-level radioactive waste (HLW) from a variety of processes. Unfortunately, waste transfer records were incomplete. Chemical reactions going on in the tanks were not totally understood. Every tank had high concentrations of powerful oxidizers in the form of nitrates and nitrites, and some tanks had relatively high concentrations of potential fuels that could react explosively with oxidizers. A few of these tanks periodically released large quantities of hydrogen and nitrous oxide, a mixture that was potentially more explosive than hydrogen and air. Both the nitrate/fuel and hydrogen/nitrous oxide reactions had the potential to rupture a tank exposing workers and the general public to unacceptably large quantities of radioactive material. One tank (241-C-106) was generating so much heat that water had to be added regularly to avoid thermal damage to the tank's concrete exterior shell. The tanks contained more than 250 million Curies of radioactivity. Some of that radioactivity was in the form of fissile plutonium, which represented a potential criticality problem. As awareness of the potential hazards grew, the public and various regulatory agencies brought increasing pressure on DOE to quantify the hazards and mitigate any that were found to be outside accepted risk guidelines. In 1990, then Representative, now Senator Ron Wyden (D-Oregon), introduced an amendment to Public Law 101-510, Section 3137, that required DOE to identify Hanford tanks that might have a serious potential for release of high-level waste

Parto pretermine nelle gravidanze complicate: nuove strategie diagnostiche e terapeutiche

Parto pretermine nelle gravidanze complicate: nuove strategie diagnostiche e terapeutiche. Il parto pretermine rappresenta una complicanza ostetrica di rilevante entità, interessando il 5-10% delle gravidanze. E’ considerato ormai la principale causa di morbilità e mortalità perinatale e neonatale nei paesi sviluppati, contribuendo al 50-70 % di tutte le morti neonatali. Nelle gravidanze singole, la percentuale di parto prima della 32° settimana è dell’1-2% mentre è pari al 5-10% nelle gravidanze gemellari. E’ evidente che, considerata l’ampiezza del fenomeno, strategie di prevenzione del parto pretermine diventino sempre più fondamentali. Tuttavia, malgrado il notevole interesse prestato dai ricercatori negli ultimi decenni, non si è ottenuta una riduzione sensibile dell’incidenza del parto pretermine, probabilmente a causa dell’ampia disomogeneità nei comportamenti preventivi, nei protocolli terapeutici e nella individuazione e valutazione dei fattori di rischio. L’impiego dell’ecografia per lo studio della biometria e della dinamica della cervice uterina durante la gravidanza è diventata, nell’ultima decade, un importante aiuto nel controllo ostetrico prenatale per l’identificazione delle pazienti ad alto rischio di parto pretermine. In tal senso, un ruolo cruciale sembra essere svolto dalla misurazione ecografia transvaginale della lunghezza cervicale durante il secondo trimestre di gravidanza. Le linee di ricerca seguite sono state tre. 1) Atosiban versus cerchiaggio cervicale nelle pazienti con gravidanza gemellare a rischio di parto pretermine. Nostra esperienza. Nell’ambito di questo studio è stato affrontata la problematica del parto pretermine nelle gravidanze gemellari confrontando l’approccio terapeutico chirurgico con quello non chirurgico. L’obiettivo è stato valutare l’efficacia, in termini di epoca gestazionale al parto, della terapia con Atosiban, antagonista recettoriale dell’ossitocina, rispetto al cerchiaggio cervicale preventivo, nelle gravidanze gemellari a rischio di parto pretermine. Una lunghezza cervicale < 25mm è stata l’indicazione al trattamento, in quanto considerata a rischio di parto pretermine. I risultati dello studio hanno dimostrato come il trattamento con Atosiban nelle gravidanze gemellari a rischio di parto pre-termine sia da preferire al cerchiaggio preventivo. Tale dato è verosimilmente riconducibile al meccanismo d’azione del farmaco, il quale oltre ad antagonizzare l’azione dell’ossitocina, agisce indirettamente anche sul rilascio delle prostaglandine, intervenendo, quindi anche sui meccanismi biochimici che concorrono al fenomeno del ripening cervicale. Di contro, il cerchiaggio cervicale svolge esclusivamente un’azione meccanica, il cui utilizzo, non è stato validato da studi clinici randomizzati controllati. 2) Ripetizione del trattamento con Atosiban nelle gravidanze gemellari. Nostra esperienza. La percentuale di parto pretermine è dell’1-2% nelle gravidanze singole mentre è pari al 5-10% nelle gravidanze gemellari. La valutazione della lunghezza cervicale con ecografia transvaginale identifica con buona sensibilità le pazienti a rischio. L’atosiban rappresenta il tocolitico di prima scelta, in quanto dotato di minori effetti collaterali rispetto agli altri tocolitici, in particolare in tali gravidanze, non aumenta il rischio di edema polmonare. Nelle gravidanze gemellari non sempre un singolo trattamento con atosiban è efficace. Scopo dello studio è stato, valutare l’effetto di una sua ripetizione nelle gravidanze gemellari con persistente rischio. Nelle gravidanze gemellari è ipotizzabile un maggior rilascio di ossitocina o una maggiore espressione dei suoi recettori tale da superare l’azione antagonista del farmaco, che non risulterebbe efficace se somministrato alla dose standard. I risultati dello studio dimostrano come il monitoraggio della lunghezza cervicale e l’eventuale ripetizione del trattamento con Atosiban nelle gravidanze gemellari a rischio di parto pretermine prolunghi la durata della gravidanza. 3. Parto pretermine e patologie autoimmuni. Nostra esperienza. Le malattie autoimmuni sono 5 volte più frequenti nelle donne, raggiungono un picco di incidenza nella vita riproduttiva. Le gravide affette da tali patologie sono ad elevato rischio di complicanze. In questo studio è stata valutata la percentuale di alta positività degli ANA in pazienti con minaccia di parto pretermine con e senza pPROM. Vari studi in letteratura hanno dimostrato come il parto pretermine è più frequente nelle donne affette da malattie autoimmuni rispetto ai controlli (12% rispetto a 4%) e come la rottura prematura delle membrane sia più frequente in tali gravidanze, verificandosi nel 39% dei casi rispetto al 2-5% della popolazione generale. Gli ANA sono presenti nel 98% dei casi di patologia autoimmune, il test di immunofluorescenza per gli ANA è usato come test di screening alla valutazione iniziale di un paziente con sospetta patologia autoimmune. Tale studio mostra come nelle pazienti ANA positive ci sia una maggiore incidenza di pPROM. Probabilmente i fattori coinvolti sono legati allo stato infiammatorio cronico determinato dalla patologia autoimmune di base che agirebbe sia sulla componente connettivale delle membrane amniotiche indebolendone la struttura, sia attraverso un aumento delle citochine proinfiammatorie locali di cui è nota l’ezipatogenesi nel parto pretermine. Uno screening autoimmune nelle pazienti con minaccia di parto pretermine e pPROM potrebbe essere consigliato

Parto pretermine nelle gravidanze complicate: nuove strategie diagnostiche e terapeutiche

La problematica del parto pretermine nella attuale medicina perinatale in gravidanze singole, gemellari, nelle patologie autoimmuni con applicazioni cliniche e di ricerca