Human malignancy-associated nucleolar antigen as a marker for tumor cells in patients with acute leukemia

Tumor burden in adult patients with acute leukemia is assessed using the percentage of blast cells in the bone marrow or blood. It is clear, however, that not all blast cells are leukemic cells, especially during rapid marrow regeneration. Similarly, some leukemia cell lines have been shown to differentiate in vitro, and the same process also occurs in vivo. Therefore, the leukemic burden may be due to more differentiated cells as well as to blast cells. The purpose of this study was to investigate whether the human malignancy-associated nucleolar antigen (HMNA) could be used as a marker for leukemic cells and to examine its potential as a diagnostic tool. The proportion of HMNA-positive cells in the bone marrow of patients with acute leukemia was determined by indirect immunofluorescence with antibodies to HMNA and was compared with the differential counts routinely made in the clinic laboratory. The percentages of HMNA-positive cells among the nucleated cells in the marrow of 72 patients with clinical evidence of leukemia were significantly higher (range 9%-98%, median 83%) than those observed for nonleukemic individuals (range less than 0.05%-2.5%, median 1%) or for fractions of marrow cells from normal volunteers enriched for normal early progenitor cells (less than or equal to 2%). Patients with leukemia in remission had a lower percentage of HMNA- positive cells (range 0%-83%, median 3%). The percentage of HMNA- positive cells increased as patients approached relapse. Although the percentage of HMNA-positive cells was related to the percentage of blast cells in the bone marrow of the patients with leukemia, some partially differentiated cells were also HMNA-positive in some specimens, and some blastic cells were HMNA-negative in other specimens. These studies indicate the potential usefulness of HMNA as a marker for leukemic cells.     

Safety and pharmacokinetics of multiple doses of recombinant human CuZn superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome

OBJECTIVES: To examine the safety and pharmacokinetics of multiple intratracheal (IT) doses of recombinant human CuZn superoxide dismutase (rhSOD) in premature infants with respiratory distress syndrome who are at risk for developing bronchopulmonary dysplasia (BPD). Methods. Thirty-three infants (700 to 1300 g) were randomized and blindly received saline, 2.5 mg/kg or 5 mg/kg rhSOD IT within 2 hours of surfactant administration. Infants were treated every 48 hours (as long as endotracheal intubation was required) up to 7 doses. Serial blood and urine studies, chest radiographs, neurosonograms, SOD concentration and activity measurements, and tracheal aspirate (TA) inflammatory markers were assessed throughout the 28-day study. RESULTS: SOD concentrations in serum (0.1 [0.05/0.15] microg/mL-geometric mean with lower/upper confidence intervals), tracheal aspirates (TA) (0.2 [0.1/0.3] microg/mL) and urine (0.3 [0.2/0.4] microg/mL) were similar at baseline in all 3 groups and did not change significantly in the placebo group. In the rhSOD treatment groups, SOD concentrations were increased on day 3 and did not change significantly thereafter over the 14-day dosing period (also measured on days 5, 7, and 13). SOD concentrations averaged 0.4 [0.3/0.5] microg/mL in serum, 0.8 [0.6/1.2] microg/mL in TA and 1.1 [1.0/1.3] microg/mL in urine for the low-dose group and 0.6 [0.5/0.7] microg/mL in serum, 1.1 [0.9/1.5] microg/mL in TA, and 2.2 [1.6/2.9] microg/mL in urine for the high-dose group over the 14-day dosing period. Enzyme activity directly correlated with SOD concentration and rhSOD was active even when excreted in urine. TA markers of acute lung injury (neutrophil chemotactic activity, albumin concentration) were lower in the rhSOD agroups compared with placebo. No significant differences in any clinical outcome variable were noted between groups. CONCLUSIONS: These data indicate that multiple IT doses of rhSOD increase the concentration and activity of the enzyme in serum, TA and urine, reduce TA lung injury markers and are well-tolerated. Further clinical trials examining the efficacy of rhSOD in the prevention of BPD are warranted.     

The impact of glucose-insulin-potassium infusion in acute myocardial infarction on infarct size and left ventricular ejection fraction [ISRCTN56720616]

Background

Stopping antipsychotic treatment can interrupt improvement and exacerbate the illness. The reasons for discontinuing treatment during controlled clinical trials were analyzed to explore this phenomenon.

Methods

A post-hoc, pooled analysis was made of 4 randomized, double-blind clinical trials, 24–28 weeks in duration, involving 1627 patients with schizophrenia or a related disorder. Analyses combined all the atypical antipsychotic treatment groups in the studies.

Results

The majority of patients (53%) stopped their treatment at an early stage. Poor psychiatric response along with worsening symptoms was the most frequently given reason for discontinuing the course (36%), which was substantially more common than discontinuation due to poor tolerability of the medication (12%). This phenomenon was corroborated by less improvement in patients who discontinued treatment compared with those who completed, based on the PANSS total scores. Discontinuation due to poor response was, apparently, more predominantly linked to patient perception than to physicians' conclusions alone (80% vs. 20%). Discontinuation due to patient perception of poor response appeared to occur particularly early in the course of treatment. Patients who discontinued due to poor toleration of the medication responded in a more comparable manner with completers.

Conclusion

Discontinuing treatment may lead to exacerbation of symptoms, undermining therapeutic progress. In these studies, poor response to treatment and worsening of underlying psychiatric symptoms, and to a lesser extent, intolerability to medication were the primary contributors to treatment being discontinued. Our findings suggest that adherence may be enhanced by effective symptom control, as objectively measured and as subjectively perceived. Such strategies may improve patients' willingness to undertake long-term therapy and increase the likelihood of a better prognosis.     

Inactivation of lipid-enveloped and non-lipid-enveloped model viruses in normal human plasma by crosslinked starch-iodine

BACKGROUND: The purpose of this study was to evaluate an iodine-based method of activating potentially harmful viruses that might be found in normal human plasma. STUDY DESIGN AND METHODS: A procedure has been developed for inactivating lipid-enveloped and non-lipid-enveloped model viruses in normal human plasma by using iodine complexed to crosslinked potato starch. The established conditions are an iodine concentration of 1.05 mg per mL and 60 minutes' incubation. RESULTS: Under these conditions, inactivation of more than 9 log10 of vesicular stomatitis virus, a lipid-enveloped virus, and more than 7 log10 of encephalomyocarditis virus, a non-lipid-enveloped virus, was achieved, with minimal losses of biologic activity of selected plasma proteins. Under these conditions, 70 percent of factor VIII activity, 77 percent of factor IX activity, and 100 percent of protein C activity in the plasma were retained. CONCLUSION: Crosslinked starch-iodine may be useful in the inactivation of viruses in single-donor plasma units and in pooled human plasma before fractionation.     

Head and neck MR imaging in the pediatric patient

Magnetic resonance (MR) imaging studies of the head and neck (excluding the brain) were obtained in 49 children believed to have lesions of the head and neck. Seven children had normal images; in the remaining 42, lesions were divided into four categories: midline lesions, lesions of symmetric paired structures, facial lesions, and nasopharyngeal and oropharyngeal lesions. All entities were well delineated by MR imaging. The imaging planes and sequences chosen depended on the suspected abnormality. Midline lesions were best imaged in the sagittal plane, lesions of paired structures and the face in the axial or coronal planes, and nasopharyngeal and oropharyngeal lesions in the axial or sagittal planes. Intracranial extension of head and neck neoplasms was best evaluated in the coronal plane. Surface coils provided better resolution and were thus more useful in evaluating small superficial lesions; head or body coils were more useful in defining the extent of large lesions. T2-weighted images provided better differentiation between normal and tumor tissue in patients with head and neck neoplasms.     

Design and implementation of GRIP: a computerized glucose control system at a surgical intensive care unit

Background  

Tight glucose control by intensive insulin therapy has become a key part of critical care and is an important field of study in acute coronary care. A balance has to be found between frequency of measurements and the risk of hypoglycemia. Current nurse-driven protocols are paper-based and, therefore, rely on simple rules. For safety and efficiency a computer decision support system that employs complex logic may be superior to paper protocols.     

Testicular tumors: prospective analysis of real-time US patterns and abdominal staging

Echomorphologic features of 57 testicular lesions (48 neoplasms, nine benign lesions) were analyzed prospectively by means of high-resolution real-time ultrasonography (US). There was a broad spectrum of texture patterns for testicular malignancies, 92% of which exhibited a predominantly decreased echogenicity compared with that of normal tissue. US findings alone could not be used to make a specific prediction of malignant disease or to classify a neoplasm histologically. However, different kinds of tumors exhibited characteristic echomorphologic features that corresponded to their gross morphologic appearance; a knowledge of these echomorphologic features is extremely useful for the US differentiation of tumors from nonneoplastic scrotal pathologic conditions. All neoplasms in this series displayed distinct abnormalities in parenchymal texture, and all were detected with US. The sensitivity and predictive value of a normal sonogram were as high as 100%. With regard to the detection of retroperitoneal lymph node metastases from testicular tumors, abdominal US had an overall accuracy rate of 96% and was of superior diagnostic value compared with bipedal lymphangiography.     

Computed tomography and radionuclide imaging in the evaluation of ischemic stroke

One hundred forty-one patients with cerebral or cerebellar infarction were examined by computed tomography (CT) as soon after the ictus as possible. The examination was repeated in 7 days, and a radionuclide brain scan was performed. The overall detection rate for ischemic infarction was approximately equal for both techniques, ranging from 58% for radionuclide scanning to 66% for the delayed CT. Almost half of the supratentorial infarcts examined by CT on the day of the ictus were demonstrated. Mass effect was observed as early as the first day and as late as the 25th day.