Follicular bronchiolitis in association with connective tissue diseases

Eleven patients with connective tissue diseases were found to have bronchiolar lesions associated with minimal or no alveolar septal thickening. Seven of these patients had rheumatoid arthritis, 3 had Sjögren’s syndrome, and 1 had ankylosing spondylitis. Radiographic studies showed an interstitial pattern in all patients. The patients were nonsmokers and received no treatment prior to biopsy. All lung biopsy specimens showed inflammatory bronchiolar lesions which consisted of bronchiolar and peribronchiolar lymphocytic infiltrates (follicular bronchiolitis). The bronchiolar lesion has been reported previously in patients with connective tissue diseases treated with D-penicillamine; whether it represents a component of the systemic disease or a lack of effect of the therapeutic agent had not been established. The present study shows that several connective tissue diseases can be associated with inflammatory bronchiolar lesions.     

Heterogeneity of B cell involvement in acute nonlymphocytic leukemia

In order to study the pattern of B cell involvement in acute nonlymphocytic leukemia (ANLL), multiple B lymphoid cell lines were established by Epstein-Barr virus transformation of peripheral blood mononuclear cells from two patients with the disease who were heterozygous for the X chromosome-linked glucose-6-phosphate dehydrogenase (G6PD). In one patient, the progenitor cells involved by the leukemia exhibited multipotent differentiative expression, whereas in the other patient the cells showed differentiative expression restricted to the granulocytic pathway. In the patient whose abnormal clone showed multipotent expression, the ratio of B-A G6PD in B lymphoid cell lines was skewed in the direction of type B (the enzyme characteristic of the leukemia clone) and significantly different from the 1:1 ratio expected. It is, therefore, likely that the neoplastic event occurred in a stem cell common to the lymphoid series as well as to the myeloid series. In contrast, evidence for B cell involvement was not detected in the patient whose ANLL progenitor cells exhibited restricted differentiative expression. These findings underscore the heterogeneity of ANLL. Clinically and morphologically similar malignancies in these two patients originated in progenitors with different patterns of stem cell differentiative expression. This difference may reflect differences in cause and pathogenesis.     

Use of multiple T cell-directed intact ricin immunotoxins for autologous bone marrow transplantation

The monoclonal antibodies (MoAb) T101, G3.7, 35.1, and TA-1 were conjugated to intact ricin using a thioether linkage. These MoAb detect, respectively, the CD5[gp67], CD7[p41], CD2[p50], and [gp95, 170] determinants that are found in the vast majority of cases of T cell acute lymphocytic leukemia (T-ALL). The resulting immunotoxins (ITs) and an equimolar mixture of these ITs were evaluated as potential purgative reagents for autologous transplantation in T-ALL. Leukemic cell lines were used to compare the kinetics of protein synthesis inactivation mediated by each IT. The cells were treated with IT in the presence of lactose in order to block the native binding of ricin. The observed rates of protein synthesis inactivation correlated with target antigen expression detected by fluorescence-activated cell sorter analysis. Of the four ITs, T101-ricin (T101-R) exhibited the fastest rate of inactivation, followed in order by G3.7-ricin, TA-1-ricin, and 35.1-ricin. At concentrations greater than 300 ng/mL, a cocktail containing an equimolar amount of all four ITs (referred to as the four- IT cocktail) exhibited kinetics that were as fast or faster than those of T101-R. The long-term cytotoxic effects of individual ITs and the four-IT cocktail were evaluated using a sensitive clonogenic assay. Each IT was specifically cytotoxic and inhibited 1 to 4 logs of clonogenic leukemic cells at doses (300 to 600 ng/mL) that can be used clinically. The four-IT cocktail was highly cytotoxic; a concentration of 300 ng/mL inhibited greater than 4 logs of leukemic cells while sparing the majority of committed (CFU-GM, CFU-E) and pluripotent (CFU- GEMM) hematopoietic stem cells. The determination of both short-term kinetics of protein synthesis inactivation and longer-term inhibition of clonogenic growth allowed new insight into cell killing by IT. Our results suggest that ITs continue to act on clonogenic target cells for a period of three to five days. Interestingly, the four-IT cocktail was not as potent against clonogenic leukemic cells as T101-R alone, although it exhibited kinetics of protein synthesis inhibition that were as fast as those of T101-R alone. This finding suggests that internalized ITs may differ in the length of time they remain active within the cell. Our results also demonstrate the importance of using several different assays to evaluate IT reagents.     

Hemodynamic effect of hydralazine in interstitial lung disease patients with cor pulmonale. Immediate and short-term evaluation at rest and during exercise

Hydralazine was administered short-term to 13 patients who had stable interstitial lung disease (ILD), pulmonary arterial hypertension (PAH); mean pulmonary arterial pressure ( [PAP]=26 +/- 9 mm Hg), and cor pulmonale (CP). All patients were studied at rest and during exercise. After intravenous hydralazine at rest, there were statistically significant increases in cardiac index (CI) (p less than 0.001), arterial oxygen saturation (SaO2) (p less than 0.01), and mixed venous saturation (S-vO2) (p less than 0.01). Pulmonary vascular resistance (Rp) (p less than 0.005) and systemic resistance (Rs) decreased (p less than 0.001), and PAP did not change. During exercise, PAP did not change; however, CI (p less than 0.01), PaO2 (p less than 0.001), and S-vO2 (p less than 0.01) increased further. The increase in Rp was significantly reduced (p less than 0.01). After continuation of oral hydralazine therapy in 12 patients for 7 days, PAP at rest was not statistically different from control; Rp and Rs remained decreased (p less than 0.001). The same results were found for CI, PaO2, S-vO2, and Rs during exercise. Although PAP did not change from control values, the drug significantly reduced the increase in Rp (p less than 0.005). Vasodilator therapy with hydralazine could be useful in patients with stable ILD who have inflammation with minimal to moderate fibrosis and PAH and might be used as an adjunct to conventional therapy for ILD and CP.     

Ultrasound-guided infraclavicular axillary vein cannulation

Background and objectivePercutaneous central venous cannulation is a challenging procedure. Traditionally, an external landmark technique has been used to identify puncture site. We wanted to evaluate an ultrasound-guided technique for the axillary vein cannulation, looking specifically at the ease of use, success rate and decreased complications.MethodsSixty consecutive surgical patients scheduled for central venous catheter placement were registered. An ultrasound scanner made for guiding an in plane puncture of axillary vein was used. After locating the vessels, an echo-guided sterile procedure was performed to cannulate the vein.ResultsCannulation was successful in all patients, and there were no complications during insertion of the catheters. Both axillary veins were cannulated, and the vein was punctured successfully at first attempt in 95% of the patients. The median time from the start of the first puncture (of the skin) until the aspiration of blood was 15 (7– 135) seconds.ConclusionThis ultrasound-guided technique for inserting central venous catheters in axillary vein was easy to apply. This procedure could increase precision and safety in patients undergoing axillary vein cannulation.     

Effect of oral glucose administration on ghrelin levels in obese children

OBJECTIVE: Coexpression of GH secretagogue receptor and ghrelin in the pancreas suggests that this peptide is involved in glucose metabolism. Previous reports in adult humans have demonstrated that plasma ghrelin levels decrease after oral glucose administration. However, no data are available in children. Therefore, the aim of this study was to analyze the response of plasma ghrelin levels in obese children after oral glucose administration. SUBJECTS AND METHODS: Twenty-eight obese children ranging from Tanner I to Tanner V were studied. All subjects were given 0.75 g/kg (maximum 75 g) glucose solution after overnight fasting. Ghrelin, insulin, glucose and IGF-binding-protein-1 were determined at 0, 30, 60 and 120 min of the oral glucose tolerance test (OGTT). RESULTS: Basal plasma ghrelin levels were significantly lower than in the respective control groups. These levels decreased significantly during OGTT in obese children, reaching a nadir of 28+/-9% at 60 min in parallel with the maximum increase in glucose levels and previous to maximum insulin levels. CONCLUSION: The rapid fall in plasma ghrelin concentration in obese children after glucose load suggests a mechanism for the control of appetite after food intake.     

X-linked chronic granulomatous disease: correction of NADPH oxidase defect by retrovirus-mediated expression of gp91-phox

Chronic granulomatous disease (CGD) is an inherited immunodeficiency resulting from the inability of an individual's phagocytes to produce superoxide anions because of defective NADPH oxidase. The disease may be treated by bone marrow transplantation and as such is a candidate for somatic gene therapy. Two thirds of patients have defects in an X- linked gene (X-CGD) encoding gp91-phox, the large subunit of the membrane cytochrome b-245 component of NADPH oxidase. Epstein-Barr virus-transformed B-cell lines from patients with CGD provide a model system for the disease. We have used retrovirus-mediated expression of gp91-phox to reconstitute functionally NADPH oxidase activity in B-cell lines from three unrelated patients with X-CGD. The protein is glycosylated and membrane associated, and the reconstituted oxidase is appropriately activated via protein kinase C. The kinetics of superoxide production by such reconstituted cells is similar to that of normal B-cell lines. These data show the potential of gene therapy for this disease.