IL-5 is required for eosinophil recruitment, crystal deposition, and mononuclear cell recruitment during a pulmonary Cryptococcus neoformans infection in genetically susceptible mice (C57BL/6)

CBA/J (highly resistant), BALB/c (moderately resistant), and C57BL/6 (susceptible) mice displayed three resistance patterns following intratracheal inoculation of Cryptococcus neoformans 52. The inability to clear the infection correlated with the duration of the eosinophil infiltrate in the lungs. The role of IL-5 in promoting the pulmonary eosinophilia and subsequent inflammatory damage in susceptible C57BL/6 mice was investigated. C57BL/6 mice developed a chronic alveolar, peribronchiolar, and perivascular eosinophilia following C. neoformans infection. This resulted in the accumulation of intracellular Charcot-Leyden-like crystals in alveolar macrophages by wk 4 and the extracellular deposition of these crystals in the bronchioles with associated destruction of airway epithelium by wk 6. IL-5 mRNA was expressed in the lungs, and injections of anti-IL-5 mAb prevented eosinophil recruitment and crystal deposition but did not alter cryptococcal clearance. Depletion of CD4+ T cells (but not CD8+) ablated IL-5 production by lung leukocytes in vitro and eosinophil recruitment in vivo. Neutralization of IL-5 also inhibited the recruitment of macrophages, CD8+ T lymphocytes, and B lymphocytes by 47 to 57%. Anti-IL-5 mAb inhibited CD4+ T lymphocyte recruitment by 30% but did not affect neutrophil recruitment. Thus, the development of a chronic eosinophil infiltrate in the lungs of C. neoformans-infected C57BL/6 mice is a nonprotective immune response that causes significant lung pathology. Furthermore, IL-5 promotes the recruitment and activation of eosinophils, resulting in the recruitment of additional macrophages and lymphocytes into the lungs.     

Pigmented uveal tumours in a transgenic mouse model

Lectins are sensitive probes which bind carbohydrate structures specifically. In this study, we modified the lectin staining procedure for sensitive detection of carbohydrate structures in formalin-fixed, paraffin-embedded sections of normal and heterologous serum-induced fibrotic livers. The liver sections were heated in hot distilled water at 100 degrees C for 10 min (thermo-treatment: TT), and then stained with 24 different lectins. In comparison with the results from sections without TT (nonTT), enhanced and/or alternated staining patterns of 19 lectins were demonstrated in sections with TT, and enhanced staining of Vicia villosa agglutinin seen in Kupffer cells was noted. Interestingly, no positive staining was seen with Dolichos biflorus agglutinin, peanut agglutinin or soybean agglutinin (SBA), which recognize O-linked carbohydrate chains, in Kupffer cells of non-TT sections, but strong positive staining was demonstrated in those of TT sections. SBA-positive staining in the cytoplasm of some scattered hepatocytes located in the periportal and perifibrous zones and central zone of pseudolobules was demonstrated only in the fibrotic liver sections with TT. Such findings indicate the heterogeneity of hepatocytes in the liver with fibrosis. Formalin fixation causes masking of lectin binding sites, especially O-linked carbohydrate chains, and TT may recover such masking reactions. TT improved the staining reactions for many lectins in formalin-fixed, paraffin-embedded liver sections, and new staining patterns appear after TT. Modified TT staining procedures may be useful for the diagnosis and prognosis of liver fibrosis.     

Direct endoscopic percutaneous jejunostomy (EPJ). Clinical results

Direct puncture of the small bowel under endoscopic guidance (direct EPJ) is possible in patients whose stomach has been removed or whose small bowel cannot be punctured by other methods. From January 1990 to June 1992 a total of 39 patients underwent successful direct EPJ at our institution. The indications were malnutrition after partial or total gastrectomy (n = 19), insufficient anastomosis or a stenosis after esophageal resection and esophagojejunostomy (n = 13), esophageal perforation (n = 3), fistulas (n = 2), or severe trauma (n = 2). The tubes were inserted at the bedside under local anesthesia using the string pull-through technique. The procedure was attempted in five other patients but it was technically impossible to insert the tubes in these patients. Postoperative enteral feeding was possible in all 39 patients whose direct EPJ was successful. Complications included tube dysfunction due to plugging and fracture in five patients, pressure-induced enteric ulcers in two, and local infections in three patients. The ulcers and infections were managed conservatively. We conclude that direct EPJ is a safe, effective alternative to surgical catheter-jejunostomy.     

Three-dimensional respiratory-gated MR angiography of coronary arteries: comparison with conventional coronary angiography

OBJECTIVE: MR coronary angiography is most often performed using two-dimensional techniques. Although three-dimensional (3D) acquisitions do have important advantages, they take too long for a single breath-hold and are thus susceptible to respiratory motion artifacts. The purpose of this study was to investigate the accuracy of a unique respiratory-gated 3D MR angiographic technique in identifying the proximal coronary arteries in patients suspected of having coronary artery disease. In addition, we investigated the capability of this technique to detect proximal stenoses. SUBJECTS AND METHODS: We performed a prospective blinded study in 20 patients who were referred for conventional coronary angiography. A cardiac-gated 3D gradient-echo sequence with fat suppression was used. Retrospective respiratory gating was performed using navigator echoes of the diaphragm position. Using multiplanar reformatting, two independent readers blindly analyzed the data sets for visualization of major coronary arteries, lengths of imaged segments, and detection of significant stenoses (> 50% occlusion of the luminal diameter by conventional angiography). RESULTS: Seventy-seven of 80 (96%) coronary arteries were positively identified. In one patient, an anomalous coronary anatomy was readily identified and confirmed by conventional angiography. The average lengths of the imaged segments of the right, left main, left anterior descending, and left circumflex coronary arteries were 58 +/- 13 mm, 9 +/- 5 mm, 59 +/- 16 mm, and 24 +/- 10 mm, respectively. Overall sensitivity for the detection of stenoses was low (38%), with a specificity of 95%. Interobserver agreement was 0.92, with a kappa value of 0.65. CONCLUSION: Respiratory-gated 3D MR angiography allows accurate identification of proximal coronary arteries and may be valuable for 3D imaging of coronary anomalies. Further technical improvements are required to enhance the value of the technique in detecting stenoses.     

Eosinophil markers in seasonal allergic rhinitis. Intranasal fluticasone propionate inhibits local and systemic increases during the pollen season

BACKGROUND: The purpose was to study activation markers of the eosinophil granulocytes in seasonal allergic rhinitis, and the impact of topical steroid therapy thereupon. METHODS: Sixty-three rhinitis patients with monoallergy to grass were examined before and at peak pollen season. Blood eosinophil count, eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO) in serum and nasal lavage fluid were measured. During the season, patients were randomized to treatment with intranasal fluticasone propionate 0.1 mg o.d. (n=26), 0.2 mg o.d. (n=25), or placebo (n=12). Six healthy persons served as controls. RESULTS: During the season, all parameters, except nasal lavage ECP, increased in the placebo group (P<0.001-P<0.05). Significant differences were seen between the steroid groups and the placebo group for all parameters (P<0.001-P<0.05). Higher eosinophil count (P<0.05), serum EPO (P<0.02), and nasal lavage EPO (P<0.05) were found in patients before season than in controls. The following winter, 44 patients returned for repeated measurement. Lower levels of nasal lavage EPO were observed for patients than levels at the beginning of the season (P<0.0001). CONCLUSIONS: Intranasal fluticasone propionate reduced inflammation of the nasal mucosa, demonstrated locally by nasal lavage ECP and EPO, and systemically by blood eosinophils, serum ECP, and serum EPO. EPO seemed more sensitive than ECP as indicator of allergic inflammation. EPO demonstrated some perennial eosinophil activity in hay fever patients, increasing locally during spring.     

Knowledge and attitudes of health-care providers toward cancer pain management: a comparison of physicians, nurses, and pharmacists in the state of New Hampshire

The knowledge and attitudes toward cancer pain management of physicians, nurses, and pharmacists in the state of New Hampshire were examined through the use of a statewide survey. Many of the providers who completed the survey, and thus indicated that they treated patients with cancer pain on a regular basis, were not pain or oncology specialists. Most of these providers were quite well informed about the fundamentals of cancer pain management. Approximately 90% of providers in all three groups were not concerned about addiction among cancer patients. Yet, there was a small percentage of providers who responded in less than optimal ways to items dealing with opioid pharmacology, pain assessment, and the importance of pain relief. Comparison of responses among provider groups indicated that nurses were the most knowledgeable and pharmacists the least knowledgeable about pain assessment. Physicians were the most knowledgeable regarding opioid pharmacology but seemed the least committed to providing optimal pain relief. Further analysis identified a small group of physicians that included a disproportionately high percentage of family practitioners and surgeons who consistently responded in less than optimal ways to items dealing with the importance of pain relief. The results of this study indicate a continuing need for broad-based educational programs in cancer pain management and for new initiatives focused on practitioners who see relatively few cancer patients and may have difficulty accessing traditional educational programs.     

Phosphorous and proton spectroscopy in relation to near incarceration and incarceration of the human brain

The yeast gene, YTA10, encodes a member of a novel family of putative ATPases. Yta10p, as deduced from the nucleotide sequence, is 761 amino acids in length (predicted molecular mass 84.5 kDa). The amino acid sequence of Yta10p exhibits high similarity to two other yeast proteins, Yta11 and Yta12, and to E. coli FtsH. Several features of Yta10p are compatible with its localization in mitochondria. We report here that Yta10p is a yeast mitochondrial protein and that import is dependent on a membrane potential and accompanied by processing to a protein of approximately 73 kDa. Disruption of YTA10 leads to a nuclear petite phenotype and to a loss of respiratory competence, as shown by spectrophotometric measurement of the activities of respiratory complexes I-III and IV, respectively. These findings together with the high similarity of Yta10p to several ATP-dependent proteases suggest that Yta10p is a mitochondrial component involved, directly or indirectly, in the correct assembly and/or maintenance of active respiratory complexes.     

Molecular analysis of the retinoblastoma (RB1) gene in acute myeloid leukemia patients

Patient 1: A 48-year-old man was admitted to Osaka Red Cross Hospital because of fever and dyspnea. Laboratory examination revealed pancytopenia, liver dysfunction and hematostatic abnormality. Chest radiographs obtained on admission revealed ground-glass opacity in both lung fields, and an analysis of arterial blood showed severe hypoxemia (PaO2:46.8 Torr). Pulse therapy with methylprednisolone was started. Although the hypoxemia subsided and radiographic findings rapidly improved, pancytopenia persisted. Examination of bone marrow aspirate revealed mature histiocytes with marked hemophagocytosis. Amplified Mycobacterium tuberculosis direct tests of bronchoalveolar lavage fluid, sputum, urine, and bone marrow were all positive, and Mycobacterium tuberculosis was cultured from sputum and urine. Although the patient was taking antituberculous agents, his pancytopenia persosted. Treatment with etoposide induced remssion. Patient 2: A 19-year-old woman was admitted to Osaka Red Cross Hospital because of prolonged cough and fever. Laboratory examination revealed leukocytosis, liver dysfunction, and hematostatic abnormality. Serologic tests provided conclusive evidence of Mycoplasma infection and a CRP test was strongly positive. Chest radiographs obtained on admission revealed infiltration shadows in the middle and lower lung fields on both sides, with left pleural effusion. An analysis of arterial blood showed hypoxemia (PaO2: 54.2 Torr). Examination of bone marrow and pleural effusion samples revealed mature histiocytes with marked hemophagocytosis. Although treatment with antibiotics and pulse therapy with methylprednisolone was started, the patients respiratory functions deteriorated. Endotracheal intubation was performed. Therapy with etoposide induced remission. Hemophagocytic syndrome associated with Mycoplasma infection and tuberculosis appears to be exceedingly rare. In these 2 cases, it was difficult to achieve remission with therapy for the underlying infections, but etoposide treatment was effective.     

The Latina Breast Cancer Control Study, year one: factors predicting screening mammography utilization by urban Latina women in Massachusetts

The mechanisms underlying secondary or delayed cell death following traumatic brain injury (TBI) are poorly understood. Recent evidence from experimental models of TBI suggest that diffuse and widespread neuronal damage and loss is progressive and prolonged for months to years after the initial insult in selectively vulnerable regions of the cortex, hippocampus, thalamus, striatum, and subcortical nuclei. The development of new neuropathological and molecular techniques has generated new insights into the cellular and molecular sequelae of brain trauma. This paper will review the literature suggesting that alterations in intracellular calcium with resulting changes in gene expression, activation of reactive oxygen species (ROS), activation of intracellular proteases (calpains), expression of neurotrophic factors, and activation of cell death genes (apoptosis) may play a role in mediating delayed cell death after trauma. Recent data suggesting that TBI should be considered as both an inflammatory and/or a neurodegenerative disease is also presented. Further research concerning the complex molecular and neuropathological cascades following brain trauma should be conducted, as novel therapeutic strategies continue to be developed.