Expression and activation of erbB-2 and epidermal growth factor receptor in lung adenocarcinomas.

ErbB-2 and EGFR (epidermal growth factor receptor) are expressed in lung adenocarcinomas and associated with a poor prognosis. Immunocytochemical analysis revealed erbB-2 and EGFR coexperession as a characteristic feature of most lung adenocarcinomas, and at levels of receptor expression present in bronchial epithelial cells. In primary lung tumours and cell lines, erbB-2 detected using Western blot analysis demonstrated low-level phosphotyrosine staining of the 185 kDa band, as compared with breast cancer cell lines. A549 and A427 lung adenocarcinoma cells treated with neu differentiation factor (NDF) showed increased erbB-2 phosphotyrosine staining, but to a much lesser extent than breast cancer cells. The lung cells were examined for expression of the potential autocrine growth factors NDF and transforming growth factor alpha (TGF-alpha) by Northern blot analysis. Both NDF and TFG-alpha mRNA were abundantly expressed in the A549 cells. NDF mRNA was highest during active cell proliferation and decreased in confluent cells or after treatment with the growth-inhibitory steroid dexamethasone. Primary tumours and cell lines expressed EGFR, showing higher basal level phosphotyrosine staining than erbB-2. Treatment with NDF and EGF (epidermal growth factor) stimulated cell growth, and in A549 cells the presence of both factors provided an additive increase in cell growth. The growth stimulus that ligand-activated erbB-2 and EGFR provides to lung adenocarcinoma cells may establish a background of continued cell proliferation over which other critical transforming events may occur.     

Development of visual evoked potentials in neonates. A study using light emitting diode goggles.

We used a signal averager with light emitting diode goggles as the photostimulator to study the development of the visual evoked potentials in 40 normal neonates of between 23 and 42 weeks'' gestation. All except two infants of less than 24 weeks'' gestation had replicable visual evoked potentials. A negative peak of latency (mean (SD), 308 (21) msec) was present in all infants, but the development of the primary positive peak depended on maturity. Only infants of 37 weeks or more had a consistent positive peak of latency (mean (SD), 220 (22) msec). The practical simplicity and reliability of this technique has distinct advantages over previous conventional recording systems. Neonatal visual evoked potentials are shown to change with maturity.     

Excretion of dicarboxylic and omega-1 hydroxy fatty acids by low birth weight infants fed with medium-chain triglycerides

The effects of feeding a commercial formula containing increased amounts of medium-chain fatty acids on the urinary excretions of C6-C10 moncarboxylic, dicarboxylic, and omega-1 hydroxy acids were studied in 13 growing preterm infants of mean birth weight 1.42 kg in a randomized double-blind cross-over clinical trial. Infants were allocated to two sequential feeding regimes of 5 days each, during the last 3 days of which urine was collected and analysed by gas-chromatography mass spectrometry. The two feeding regimes consisted of high energy and protein-containing formulas specially designed for growing low birth weight infants. In one diet the triglyceride component consisted of 46% medium-chain (C8-C10) and 54% long-chain fatty acid residues: in the other it consisted of 4% medium-chain and 96% fatty acid residues. The infants were randomized so that six infants were fed first with the medium-chain predominant formula and seven were fed first with the long-chain predominant formula. There were significant differences in the urinary excretions of octanoate, sebacate, suberate, adipate, 7-hydroxyoctanoate, and 5-hydroxyhexanoate; these substances appearing in much greater quantities in the urine during the period in which medium-chain triglycerides were predominant in the formula. The significance of this organic aciduria, which accounted for 0.7% of the dietary intake of medium-chain triglycerides, remains to be established.     

Enzyme replacement therapy for infantile hypophosphatasia attempted by intravenous infusions of alkaline phosphatase-rich Paget plasma: results in three additional patients

After biochemical and radiographic studies, enzyme replacement therapy in three patients with the infantile form of hypophosphatasia was attempted by weekly intravenous infusions of bone alkaline phosphatase-rich (BAP) plasma from patients with Paget bone disease. Subsequently, circulating BAP activity was substantially increased in each patient, and in one was maintained in the normal range for nearly 2 months. Despite partial or complete correction of the deficiency of circulating BAP activity, we observed no radiographic evidence for arrest of progressive osteopenia or improvement in rachitic defects in any of the patients. Failure of infants with hypophosphatasia to show significant healing of rickets on correction of circulating BAP activity supports the hypothesis that this isoenzyme functions in situ during normal skeletal mineralization.     

Home International Normalized Ratio Monitoring: Where Evidence-Based Medicine is Exemplified in the Medicare Coverage Process

Journal of Thrombosis and Thrombolysis -     

Lung and heart-lung transplantation in patients with end-stage cystic fibrosis: the Stanford experience

BACKGROUND: Bilateral lung (BLTx) and heart-lung transplantation have gained wide acceptance as treatment of end-stage lung disease from cystic fibrosis. We reviewed our 13-year experience with thoracic transplantation for cystic fibrosis with an operative approach that favors use of cardiopulmonary bypass for BLTx. METHODS: Sixty-four patients with cystic fibrosis underwent heart-lung transplantation (n = 22, 34.4%) or BLTx (n = 42, 65.6%) between 1988 and 2000. Mean age and weight at transplantation were 29 +/- 8 years and 51 +/- 11 kg, respectively. Mean follow-up for survivors was 4.4 +/- 3.6 years. Immunosuppression regimen included cyclosporine, tapered corticosteroids, azathioprine, and induction therapy with OKT3 (murine monoclonal antibodies) or rabbit antithymocyte globulin. Cardiopulmonary bypass was used in all but 5 patients (7.8%). However, in 8 (19%) of the 42 patients having BLTx, only the grafting of the second lung was performed with cardiopulmonary bypass. RESULTS: The operative mortality rate was 1.6%. The actuarial survival rates at 1 year, 3 years, 5 years and 10 years were 93.2%, 77.7%, 61.8%, and 48.1%, respectively, with no significant difference between BLTx and heart-lung transplantation. The major hospital complications were pneumonia (n = 11, 17.2%) and bleeding (n = 8, 12.5%). Clinically significant reperfusion injury was observed in 6 patients, 3 of whom required reintubation. Freedom from acute lung rejection beyond 1 year was 47.7%. One patient underwent late retransplantation, and 4 required bronchial stenting. Obliterative bronchiolitis accounted for eight (50.0%) of 16 late deaths. CONCLUSIONS: Though postoperative bleeding and pneumonia are still of concern, satisfactory early and intermediate-term results can be expected in patients undergoing BLTx or heart-lung transplantation for cystic fibrosis. Cardiopulmonary bypass can be used for BLTx with no adverse impact on intermediate and long-term outcomes.