Fluoroquinolones in chronic obstructive pulmonary disease.
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Aged↗
Biomedical subjects
J George
Publications and source records attributed to J George.
Promoting screening mammography in inner-city settings: a randomized controlled trial of computerized reminders as a component of a program to facilitate mammography.
In a one-year randomized controlled trial, we assessed the effectiveness of a computerized mammography reminder system as a component of a program to increase the use of screening mammography in three health care organizations serving inner-city women in Detroit, Michigan (two sites of a health department, one HMO site, and two sites of a private hospital). Four thousand four hundred and one women older than 40 who had visited a study site in the preceding year were randomly assigned to one of two treatment groups. Limited intervention (LI) included physician and staff breast cancer control education, facilitated mammography appointment scheduling procedures, and elimination of out-of-pocket patient cost for mammography (at three of five sites). Full intervention (FI) included all components of limited intervention plus an additional series of "cues-to-action." These included a mammography reminder form inserted in the medical record of women who were due to have mammography, intended to increase physician referral for mammography appointments, and patient reminders intended to increase completion of mammography among referred women. During the one-year intervention period 2,725 randomized women visited a study site. The 6-month mammography appointment rates among FI women vary from 38% to 65% and the FI rate exceeds the LI rate at each site with differences from 13% (95% CI, 6 to 20) to 29% (21 to 38). The annual completed mammography rate among FI women extends from 43% to 64% and exceeds the LI rate at each site by 12% (5 to 19) to 25% (16 to 34). After age-adjustment, the mammography intervention effect sizes among the five sites were not significantly different. The average increase in FI compared to LI was 18%. The computerized reminder system is effective in increasing the use of mammography in each of the study institutions and the major effect is on physician referral for mammography.
Adult↗
The impact of microglia-derived cytokines upon gliosis in the CNS.
Injury to the CNS elicits a complex cellular response involving both astrocytes and microglia. Reactive glial populations make up the so-called 'glial scar' that has long been implicated as a barrier to axonal regeneration or as a causal factor in the genesis of epilepsy. Using in vitro models involving highly enriched populations of brain cells we have observed that astroglial growth is regulated in part by an immunomodulatory growth factor, or cytokine, called interleukin-1 (IL-1). A second cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF) serves as a potent microglial mitogen and regulator of the microglial component of the glial scar. Employing cytokines as tools to manipulate reactive gliosis, we found that IL-1 supported neuronal growth by action upon astroglia, while GM-CSF initiated epileptic-like discharges through mechanisms involving reactive microglia. We propose that a 'cytokine network' involving IL-1 and GM-CSF mediates the composition of glial scars at sites of CNS injury; these reactive glia, in turn, influence the survival and function of neighboring neurons.
Animals↗
Women's knowledge of emergency contraception.
BACKGROUND: More widespread use of emergency contraception could help to reduce the number of unwanted pregnancies. AIM: The objective of this study was to assess women's knowledge of emergency contraception. METHOD: A questionnaire was distributed to 1290 women aged between 16 and 50 years attending 14 general practice surgeries in London over a two-week period in 1990. RESULTS: The response rate was 70%. Over three quarters of the women had heard of emergency contraception; these were mainly women who used contraception, who had higher educational qualifications or who were not Muslim. Women who were the most likely to need and to use emergency contraception--those using barrier methods--had no more accurate knowledge than women using any other method of contraception. Only 53% of barrier method users knew emergency contraception could be used as a backup when other methods failed. Only one fifth of women had heard about this method from their general practitioner or any other health professional, while half had obtained their information from the media. CONCLUSION: These results suggest that including information on emergency contraception in consultations with users of barrier methods of contraception is a small step which general practitioners and practice nurses could take to increase the use of emergency contraception.
Adolescent↗
[Restriction fragment length polymorphism analysis of ventricular myosin light chain 1 gene in families with congenital heart disease].
Genomic DNAs isolated from 9 families and 13 unrelated individual patients with 4 different types of congenital heart disease were examined by Southern blot analysis using a cDNA probe which codes for the full length human ventricular myosin light chain 1. Restriction fragment length polymorphisms were detected in two families and were not associated with any type of congenital heart disease.
Blotting, Southern↗
Immunosuppressive drugs in Crohn's disease.
We review clinical experience with the immunosuppressive drugs 6-mercaptopurine (6-MP) and azathioprine, cyclosporine, and methotrexate in the management of patients with Crohn's disease. 6-MP and azathioprine are closely related structurally. Their exact mechanism of action is unknown, but both cause immunosuppression by interfering with nucleic acid metabolism in the immunological sequence that follows antigenic stimulation. 6-MP and azathioprine have proved most useful for two indications: reducing steroid requirements and healing fistulas. Among patients who are dependent on steroids for control of active inflammatory Crohn's disease, approximately 50% can be completely weaned from prednisone, and an additional 25% can tolerate a substantial dose reduction when treated with 6-MP or azathioprine. Likewise, 6-MP is effective in closing fistulas in approximately one third of patients and in reducing fistula drainage in an additional one third. However, the onset of action is slow and the results may be dose dependent. Cyclosporine, a selective immunosuppressant drug, inhibits T lymphocytes by inhibiting expression of interleukin-2 and its receptors. Its principal usefulness may be in patients with disabling fistulas or active steroid-refractory colitis who cannot tolerate the several months required for a remission induced by 6-MP or azathioprine. Methotrexate, a dihydrofolate reductase inhibitor, has antimetabolite and antiinflammatory properties. Methotrexate is only slightly, if at all, faster acting than 6-MP or azathioprine. Its principal usefulness may therefore be in cases when these other drugs have not been tolerated or are ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)
Azathioprine↗
Ulcerative appendicitis in universal and nonuniversal ulcerative colitis.
Ulcerative appendicitis (UA), the appendiceal counterpart of ulcerative colitis (UC), is frequently present in colectomy specimens from patients with universal UC and is regarded as part of the continuous inflammatory process that is a hallmark of this disease. It has been reported, although not universally accepted, that UA may also occur in UC that spares the proximal colon, constituting a skip lesion. Colectomies, which included appendices, from 160 consecutive adult and pediatric patients with UC were reviewed histologically and separated into two groups, universal and nonuniversal UC, on the basis of a stringent histopathological definition of normal mucosa. Forty-five cases with obliterated appendiceal lumens were excluded. UA was present in 82 of the 94 cases of universal UC (87%), including 75 of the 83 adult cases (90%) and 7 of the 11 pediatric cases (64%). UA was present in 18 of the 21 cases of nonuniversal UC (86%), all of which were adults, representing skip lesions. UA was found in 12 of the 14 cases in which colitis commenced distal to the hepatic flexure, including 2 of the 3 cases of left-sided colitis and 2 of the 2 cases of proctosigmoiditis. Among patients whose clinical indication for colectomy was the presence of dysplasia or carcinoma and who had patent appendices, UA was present in 6 of the 9 cases with universal UC (68%) and in each of the 3 cases with nonuniversal UC (100%). We conclude that in colectomy specimens discontinuous appendiceal involvement in nonuniversal UC is as prevalent as continuous involvement in universal UC.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Resolution of protein-losing hypertrophic lymphocytic gastritis with therapeutic eradication of Helicobacter pylori.
Lymphocytic gastritis (LG) is a recently described histological entity characterized by increased lymphocytes in the superficial gastric epithelium and foveolae. It includes a subgroup of patients with giant gastric folds and, often, a protein-losing state, a condition termed hypertrophic lymphocytic gastritis (HLG). Despite close endoscopic and clinical similarities to classical Menetrier's disease, the histopathological features of these two diseases are sufficiently distinct that they are regarded as separate entities. The etiology and pathogenesis of HLG are unknown, and the possible etiological role of Helicobacter pylori in particular is controversial. For this reason we report the case of a 48-yr-old female with HLG, hypoproteinemia, and H. pylori infection whose disease resolved clinically, endoscopically, and pathologically with therapeutic eradication of the H. pylori. H. pylori infection may be a treatable cause of at least some cases of HLG and should therefore be carefully sought in any patient with this condition.
Amoxicillin↗
Influence of membrane Ig receptor density and affinity on B cell signaling by antigen. Implications for affinity maturation.
We have initiated a series of experiments to explore the effect of changes in density of the surface Ig receptor (mIg) on Ag:mIg interactions. We transfected into the surface Ig-negative B cell line M12.4 H and L chain constructs known to effect a 10-fold change in antibody binding affinity for the naturally occurring hapten phosphocholine (PC). Two sets of stable transfectants were generated and those expressing levels of mIg comparable to the range normally seen on splenic B cells were studied. One set expressed an unmutated VH and an unmutated VL. The second set expressed the same pair of V regions except for a single somatic change in CDR3 of VH; this substitution increases the affinity of antibody for PC from 3 x 10(4) M-1 to 3 x 10(5) M-1. Ag:mIg interactions were assessed in the transfected cell lines by measuring calcium mobilization induced by stimulation with soluble PC Ag. As expected, the mutation that increased affinity for PC increased the sensitivity of transfectants to PC Ag. Relatively small changes in receptor number had a dramatic effect in the quantity and quality of a calcium response. Significantly, we found that Ag-specific signaling could occur with only a few thousand receptors per cell. Signaling differences were most noticeable with PC protein Ag (T-dependent form) compared with PC polysaccharide Ag (T-independent form). These results suggest that the down-regulation of mIg that follows B cell activation may have evolved to assist in the selection of B cell clones with higher affinity for Ag. Furthermore, the results also provide an explanation for why selection of higher affinity clones can occur with protein Ag but only poorly so with polymeric Ag.
Animals↗
Intrathrombic urokinase reverses neonatal renal artery thrombosis.
A term infant with aortic and renal artery thrombosis is described, in whom the right kidney experienced complete ischemia for 5 days. A continuous intrathrombic urokinase infusion induced complete clot lysis and reperfusion of the right kidney. Follow-up studies of renal function and renal growth have been normal. This is the first report to describe complete pharmacological salvage of a neonatal kidney after prolonged warm ischemia. This case underscores both the ability of the neonatal kidney to recover from prolonged ischemia and the need to effect thrombolysis before irreversible renal injury occurs. The intrathrombic use of fibrinolytic agents in similarly affected infants warrants consideration and further study.
Female↗
Junctional diversification in the generation of the precursor of a discrete immune response.
Phosphocholine (PC)-specific antibodies that arise in the mouse in response to Proteus morganii (PM) and use V1-DFL16.1-JH1 are characterized by a number of recurring mutations. Most striking is an invariant A for G substitution in codon 95 of VH which results in an asparagine instead of aspartate at that position. Because of the apparent importance of this substitution in an anti-PC(PM) response, we wanted to determine the molecular basis for this base change. A cDNA library derived from pre-immune splenic B cells was examined for the frequency of VDJ containing the A substitution at 95 and the presence of additional point mutations in these sequences. Six different cDNA were isolated which contained an A substitution at the VD junction (frequency 0.00009); a seventh positive cDNA could not be examined. The V segments of four of these cDNA matched known germline genes and were, therefore, unmutated. Two others closely matched V in families whose members have not all been characterized, hence, it is not known whether the mutations observed are somatic or germline in origin. Sequences of 35 cDNA clones, containing the same V segment but differing in D, J and junctional nucleotides, revealed no mutations. These results indicate that the A substitution generated at codon 95 is most likely a product of V-DJ joining.
Animals↗
Coronary risk factors in children of parents with premature coronary artery disease.
In order to assess the value of family history of premature coronary artery disease as a criterion for coronary risk factor screening, a group of 53 children with such a family history was selected. We determined various coronary risk factors in these children in comparison to 33 controls. Statistically significant differences were observed in apoprotein concentrations but not in concentrations of lipids, lipoproteins or glucose, or in blood pressure or body mass index. The ratio between apoprotein B and apoprotein AI was the best discriminator between the two groups. The predictive value of family history is more reliable for detecting abnormal apoprotein ratio than for detection of hypercholesterolemia. We conclude that if abnormal apoprotein levels during childhood are found to be a valued predictor of premature coronary artery disease, then family history of premature coronary artery disease can be used to select children for determination and assessment of their coronary risk.
Adolescent↗
Primary IgA nephropathy in adults.
IgA nephropathy was found in 9.6% of 649 adults with primary glomerulonephritis. Hypertension was detected in 51.6% and renal failure in 32.3%. A nephrotic presentation was seen in 22.6% and recurrent macroscopic hematuria in 17.7%. On light microscopy, mesangial hypercellularity and an increase in mesangial matrix were frequently seen (74.2%). Immunofluorescence studies demonstrated IgA in all patients along with C3 in 61.3%, IgM in 27.4% and IgG in 11.3%. Followup was possible in 61.3% for mean period of 17.3 months. No clinical or biochemical abnormalities were detected on followup in 26.3%. Progression to end stage renal disease was noted in 7.9%.
Adolescent↗
Moderate hypercapnia: cardiovascular function and nitrogen elimination.
Elevated carbon dioxide concentrations frequently encountered in diving operations may have cardiovascular effects. If so, changes in nitrogen loading and elimination may be induced. To study this possibility, whole body nitrogen elimination rates were determined using a rebreathing apparatus and gas chromatographic measurement of N2 in expired gas in six subjects as they breathed mixtures of 3 and 5% CO2 with 21% O2 and a balance of Ar for 125 min. No significant differences were observed among mean N2 yields, which were 815 ml (95% confidence interval +/- 51 ml), 831 ml (+/- 38 ml), and 845 ml (+/- 57 ml) for 0, 3, and 5% CO2 mixtures, respectively. Simultaneous measurements of heart rate showed a significant increase while breathing 5% CO2 as compared to 3 and 0% CO2. The increases in heart rate were not accompanied by any significant change in cardiac output, mean arterial pressure, or tissue perfusion. We conclude that at these levels of hypercarbia, tissue perfusion is not influenced enough to cause any changes in whole-body N2 elimination.
Adult↗
Antigen binding and idiotype analysis of antibodies obtained after electroporation of heavy and light chain genes encoding phosphocholine-specific antibodies: a model for T15-idiotype dominance.
Antibodies bearing the T15 idiotype dominate the murine primary immune response to phosphocholine (PC). Analysis of antigen binding of antibodies derived from V1:DFL16.1:JH1 (VH1) germline and N region-derived variant heavy (H) chains and kappa 22, kappa 24, and kappa 8 light (L) chains demonstrates that the T15H:kappa 22L (T15) antibody binds PC at least 20-40 times better than other antibodies derived from alternate germline forms of the VH1 H chain and kappa 22, kappa 24, or kappa 8 L chains. To achieve affinities in the same range as the T15 antibody, kappa 24 and kappa 8 L chain-containing antibodies must have H chains derived from variant N region or somatically mutated VH1 genes. Single amino acid differences at the VD junction of the various germline and N region variant VH1 H chains dictate the L chain that can associate with the H chain to produce a PC-specific antibody. Several H:L combinations give rise to T15 or M167 idiotype-positive antibodies that lack specificity for PC, and single amino acid substitutions or insertions at the VH1:D junction result in the loss of T15 or M167 idiotopes. Based on these observations, our data support a molecular model involving both preferential gene rearrangement and antigen-driven B cell selection to explain T15 idiotype dominance in the immune response to PC. In the absence of N region diversification, large numbers of neonatal B cells bearing the T15H:kappa 22L surface immunoglobulin M (sIgM) receptors would be selected and expanded by autologous or environmental PC antigen into the long-lived peripheral B cell pool.
Amino Acid Sequence↗
Prenatal diagnosis of tetrasomy 12p by in situ hybridization: varying levels of mosaicism in different fetal tissues.
Prenatal diagnosis of tetrasomy 12p is complicated by the discrimination of the 12p isochromosome from the duplication 21q as well as the level of mosaicism demonstrated in the particular tissue sampled. In this disease, a high percentage of chromosomally abnormal cells are generally found in fibroblastic cells, but lymphocyte karyotypes from the same individual may be normal. We report on the pregnancy of a 37-year-old female who presented to our centre at 16 weeks' gestation for genetic amniocentesis. Sonography of the fetus revealed dextrocardia and diaphragmatic hernia. Chromosome analysis of amniocytes demonstrated mosaicism of a 47,XY,+i(12p) line in 80 per cent of cells and a normal male line (20 per cent), consistent with the Pallister-Killian syndrome. Following termination, a 220 g male fetus of 18 weeks was examined. A flattened nose and low-set ears were noted. In situ hybridization with a chromosome 12 centromeric probe in lymphocytes and skin cells unequivocally confirmed the karyotype and showed the presence of a single centromere in the abnormal chromosome, suggesting a true isochromosome. Chromosome analysis of various fetal tissues was performed and the following percentages of abnormal cells were found: skin 100 per cent, chorion 50 per cent, placenta 30 per cent, and blood 80 per cent. The high frequency of tetrasomic cells in fetal blood at this early gestational age is noteworthy, since most reports of this syndrome show a very low percentage of abnormal cells postnatally.
Adult↗
Detection of feline immunodeficiency virus infection in bone marrow of cats.
Natural or experimental feline immunodeficiency virus (FIV) infection in cats is often associated with hematologic abnormalities which are similar to those observed in human immunodeficiency virus (HIV) infected patients. To determine if cells in bone marrow are infected with FIV and whether severity of hematopoietic disorder is correlated with the level of viral infection, bone marrow tissues from ten experimentally and two naturally FIV infected cats were examined by in situ hybridization for presence of FIV RNA. Seven of the 12 FIV infected cats were also naturally or experimentally coinfected with feline leukemia virus (FeLV). FIV RNA was detected mainly in megakaryocytes and unidentified mononuclear cells in the bone marrow of cats that were sick and had marrow hypercellularity and immaturity. These included all cats in the acute phase of FIV infection and two of seven long term FIV infected cats. One long term FIV infected cat with lymphosarcoma was also positive for FIV RNA in bone marrow cells. The other four long term FIV infected cats were relatively healthy, with normal bone marrow morphology, and were negative for FIV infected cells. Bone marrow from three non-infected and two cats infected with FeLV alone were also negative for FIV RNA by in situ hybridization. We concluded that megakaryocytes and mononuclear cells were targets of the viral infection and that the presence of FIV RNA in cells of the bone marrow correlated with marrow hypercellularity and immaturity, and severity of illness.
Animals↗
Delayed effects of acute oral and chronic inhalational exposure to methylparathion on learning and memory in rats.
Impairment of acquisition phase of the learning process was observed in rats even at 3 weeks after single oral exposure to the near-lethal dose of commercial grade methylparathion (MP) followed by atropine resuscitation. Though there was a trend towards memory impairment in this group of animals, memory retention was not significantly affected. Chronic inhalational exposure to MP (one exposure/day for 3 weeks) did not significantly alter learning or memory. No significant alteration in red blood cell or brain acetylcholinesterase levels were observed in either of the two groups. It appears that behavioural effects can persist even 3 weeks after exposure to acute near-lethal doses of the pesticide, as occurs in the clinical situation of suicidal attempts; while repeated exposure to no-observed-effect-level doses as occurs in farm and factory workers, may not be associated with behavioural changes.
Acetylcholinesterase↗