Inhaled lodoxamide tromethamine in the treatment of perennial asthma: a double-blind placebo-controlled study

The efficacy of lodoxamide tromethamine in the treatment of asthma was studied in a 16-week double-blind, placebo-controlled study of 68 perennial allergic subjects with asthma. Patients received either lodoxamide tromethamine, 0.25 mg four times daily, or placebo, administered by metered-dose inhaler. Response to treatment was assessed by analyzing changes in asthma symptoms, inhaled bronchodilator requirements, and pulmonary function when compared to a 2-week baseline period. Patients treated with lodoxamide tromethamine demonstrated an improvement in daytime breathing difficulty, cough, sputum production, and sleep (p less than 0.01 to 0.05), but improvement was not significantly different from that demonstrated by placebo-treated patients. Patients from both treatment groups were able to reduce their inhaled bronchodilators (p less than 0.01), but again no significant difference was apparent between lodoxamide tromethamine and placebo treatment, nor were there any differences in peak expiratory flow rate or FEV1 between the two groups. Seven patients who received lodoxamide tromethamine withdrew because of a sensation of heat and gastrointestinal symptoms. Thus, although lodoxamide tromethamine possesses potent mast cell-stabilizing activity in vitro, we have failed to demonstrate any useful long-term effect in the treatment of mild allergic asthma.     

The postnatal development of the retina in the normal and rodless CBA mouse: A light and electron microscopic study

The question of the identity of the high-affinity binding sites for progesterone with those of the corticosteroid-binding globulin (CBG) was investigated in pregnancy serum of man, rabbit, rat and mouse. Chromatographic techniques failed to separate a potential progesterone-binding macromolecule from CBG in any of the sera. Competition studies with enriched fractions containing added [³H] progesterone and [¹⁴C] cortisol strongly bound to protein showed displacement of [³H] progesterone by an excess of unlabeled cortisol, and vice versa. It is concluded that CBG is the principal progesterone binder in the pregnancy sera investigated and that no other protein with high affinity for progesterone is present in significant quantity. In contrast, the progesterone-binding globulin (PBG) in the serum of the pregnant guinea pig is distinct from CBG and has been separated from it. The PBG differed from the uterine cytosol receptor for progesterone in its sedimentation coefficient (sucrose gradient centrifugation) and its molecular size (gel filtration). With both the uterine receptor and PBG, norethynodrel displaced radiolabeled progesterone from the specific binding sites. This is in contrast to analogous binding systems involving other steroid hormones and other species, where the synthetic hormonal agent interacts strongly with the receptor protein of the target tissue, but not with the high-affinity binder in the serum.     

Cytogenetic,spectral karyotyping,fluorescence in situ hybridization,and comparative genomic hybridization characterization of two new secondary leukemia cell lines with 5q deletions,and MYC and MLL amplification

Cytogenetic studies of patients with therapy-induced acute myeloid leukemia (t-AML) have demonstrated whole chromosome loss or q-arm deletion of chromosomes 5 and/or 7 in a majority of cases. We have established two cell lines, SAML-1 and SAML-2, from two patients who developed t-AML after radiation and chemotherapy for Hodgkin disease. In both cases, the leukemia cells contained 5q deletions. SAML-1 has 58 chromosomes and numerous abnormalities, including der(1)(1qter-->1p22::5q31-->5qter), der(5)(5pter-->5q22::1p22-->1pter), +8, der(13)i(13)(q10)del(13)(q11q14.1), and t(10;11). Fluorescence in situ hybridization (FISH) with unique sequence probes for the 5q31 region showed loss of IL4, IL5, IRF1, and IL3, and translocation of IL9, DS5S89, EGR1, and CSFIR to 1p. SAML-2 has 45 chromosomes, del(5)(q11.2q31) with a t(12;13)ins(12;5), leading to the proximity of IRF1 and RB1, and complex translocations of chromosomes 8 and 11, resulting in amplification of MYC and MLL. Comparative genomic hybridization and spectral karyotyping were consistent with the G-banding karyotype and FISH analyses. Because a potential tumor suppressor(s) in the 5q31 region has yet to be identified, these cell lines should prove useful in the study of the mechanisms leading to the development of t-AML.     

A concept-based retrieval system for thoracic radiology

Current digital information systems in radiology are insufficient to accommodate the retrieval needs of academicians. Significant efforts are required in retrieving clinical cases for teaching and research. We describe a prototype system that supports intelligent case retrieval based on a combined specification of patient demographics, radiologic findings, and pathologic diagnoses. The documents for these cases can be distributed among multiple heterogeneous data bases. The system features automatic indexing of radiology and pathology reports, a comprehensive lexicon for thoracic radiology, an interface to a hospital information system, radiology information system, and picture archiving and communication systems, and a graphical user interface for query formulation and results visualization. The prototype system was developed within the domain of thoracic radiology involving patients with lung cancer.     

The Personality Assessment Inventory in individuals with traumatic brain injury.

This study examined the Personality Assessment Inventory (PAI) in 95 individuals who had suffered a traumatic brain injury (TBI). Participants were recruited from a rehabilitation hospital (n=60) and a military hospital (n=35); despite differences in demographics and injury characteristics groups did not differ on any of the clinical scales and were thus combined. In the combined group, the highest mean clinical scale elevations were on Somatic Complaints, Depression, and Borderline Features and the most common configural profiles, based on cluster analysis, were Cluster 1 (no prominent elevations), Cluster 6 (social isolation and confused thinking), and Cluster 2 (depression and withdrawal). Factor analysis indicated a robust three-factor solution that accounted for 74.86 percent of the variance and was similar to findings from the psychiatric and non-psychiatric populations in the standardization sample. The above findings are compared with the previous literature on psychopathology in TBI, particularly in regards to the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), as well as previous psychometric research on the PAI.     

Simple procedure for assessing relative quantities of neutral and acidic sugars in mucin glycoproteins: its use in assessing cyclical changes in cervical mucins.

A simple histochemical procedure for assessing relative amounts of neutral and acidic sugars in mucin glycoproteins, and its application in the study of cyclical changes of human cervical mucins, is described. This procedure, the saponification/selective periodate oxidation/borohydride reduction/alcian blue pH 2.5/periodic acid Schiff (KOH/PA*/Bh/Ab 2.5/PAS) method, uses a selective oxidation step to remove the PAS positivity of sialic acid; thus only neutral sugars stain positively with PAS, and acidic sugars (O-sulphate esters and carboxyl groups) stain with alcian blue. This differs from the KOH/Ab/PAS technique which stains sialic acid residues with both alcian blue and PAS. Applying the KOH/PA*/Bh/Ab 2.5/PAS technique to the study of cyclical changes of human cervical mucins, a decreased neutral:acidic sugar ratio in the secretory phase mucins compared with those of the proliferative phase was found. This difference was not seen with KOH/Ab/PAS staining in the same cases. The techniques and reagents used in this procedure can be easily applied in a clinical histopathology laboratory.     

Endometrial stromal tumors: an update on a group of tumors with a protean phenotype

Endometrial stromal tumors are reviewed with emphasis on their wide morphologic spectrum and problems in differential diagnosis, highlighting issues that have received particular attention in the recent literature. These neoplasms are divided into two major categories--endometrial stromal nodules and endometrial stromal sarcomas--a distinction made on the basis of the lack of significant infiltration at the periphery of the former. The division of endometrial stromal sarcomas into low-grade and high-grade categories has fallen out of favor and the designation endometrial stromal sarcoma is now considered best restricted to neoplasms that were formally referred to as "low-grade" stromal sarcoma. Endometrial sarcomas without recognizable evidence of a definite endometrial stromal phenotype, designated poorly differentiated "endometrial sarcomas," are almost invariably high grade and often resemble the mesenchymal component of a malignant mullerian mixed tumor. Two features of endometrial stromal tumors that may cause confusion are smooth muscle differentiation and epithelial patterns. Cases in the former category often have a characteristic "starburst" pattern of collagen formation. The most common epithelial patterns resemble those seen in ovarian sex-cord stromal tumors. Much less common is endometrioid gland differentiation. Some endometrial stromal tumors have a prominent fibrous or myxoid appearance and the myxoid tumors should be distinguished from myxoid leiomyosarcoma. Other unusual features of endometrial stromal tumors are also discussed. Lesions in the differential diagnosis of uterine endometrial stromal neoplasms include highly cellular leiomyoma, cellular intravenous leiomyomatosis, adenomyosis with sparse glands, metastatic carcinoma, and lymphoma. Endometrial stromal sarcomas at extrauterine sites may be primary or metastatic from a uterine tumor, the latter sometimes being occult and difficult to definitively establish, particularly if there is a history of a remote hysterectomy for "leiomyomas." Endometrial stromal sarcomas of the ovary, whether primary or metastatic, may be difficult to distinguish from ovarian sex-cord stromal tumors. Extragenital endometrial stromal sarcomas may be confused with diverse lesions such as gastrointestinal stromal tumors, hemangiopericytoma, lymphangiomyomatosis, or mesenchymal cystic hamartoma of the lung. Immunohistochemistry may play a role in evaluating these tumors and in some instances establishing the diagnosis although conventional light microscopic analysis suffices in the majority of cases. The unusual tumor, the "uterine tumor resembling an ovarian sex-cord tumor," is also considered in this review as it is almost certainly of endometrial stromal derivation in many cases. These neoplasms may have a striking resemblance to granulosa cell tumors or Sertoli cell tumors, including those with a retiform pattern, and have recently been shown to be frequently inhibin positive.     

Interaction of bromocriptine and cyclosporine in insulin dependent diabetes mellitus: Results from the Canadian open study

Although cyclosporine A (Cy-A) is effective in modifying the initial course of newly diagnosed insulin dependent diabetes mellitus (IDDM) it has a number of side effects, particularly renal, which limit its use. In this study we investigated the potential synergistic effects of bromocriptine (BCR) therapy in treating patients with newly diagnosed IDDM. Three groups of patients were treated: (1) fourteen patients on Cy-A who required a decrease in their dose due to elevated creatinine; (2) four newly diagnosed patients whose initial therapy consisted of low dose (5 mg/kg/day) Cy-A and 10 mg/day of BCR; (3) eight patients whose glucagon-stimulated connecting-peptide (C-peptide) levels were greater than 0.3 nmol/l but whose insulin requirements were over 0.3 U/kg/day and whose Cy-A was to be discontinued. The results suggest that there was no statistically significant difference in stimulated C-peptide, glycosylated haemoglobin, daily insulin dose or serum creatinine. However, the trend suggested that BCR may have some protective effect on preserving endogenous insulin secretory capacity, although glycosylated haemoglobin and daily insulin dose increased. The results do not suggest that patients with newly diagnosed IDDM significantly benefit from concurrent BCR and Cy-A therapy.     

Characterization of major histocompatibility antigens on trinitrophenyl-modified cells.

Cell membrane proteins encoded for by the major histocompatibility complex (MHC)¹ are associated with the antigenic determinant(s) recognized on trinitrophenyl (TNP)-modified cells by syngeneic murine cytotoxic T lymphocytes and by hapten-reactive guinea pig T cells. To investigate the relationship of the TNP moiety on TNP-modified cells to these major histocompatibility antigens, peritoneal exudate cells or splenocytes from two inbred guinea pig strains and one inbred murine strain were TNP-modified, radioiodinated and lysed in detergent. TNP-derivatized proteins were then isolated using an anti-TNP immunoabsorbent, and the presence on TNP-derivatized histocompatibility antigens in the eluted proteins was determined by immunoprecipitation experiments and SDS-polyacrylamide gel electrophoretic analysis. Whereas most of the various histocompatibility antigens examined were found to be TNP-derivatized in amounts proportional to the degree of membrane protein derivation as a whole, only small amounts of TNP-modified strain 2 guinea pig Ia antigens were found, and no hapten-modified strain 13 guinea pig Ia antigens were detected. It is concluded that, in contrast to most MHC gene products, strain 13 Ia antigens are not derivatized on TNP-modified cells and, thus, represent an important exception demonstrating that histocompatibility antigens need not be directly TNP-derivatized for T cell recognition and activation.