[Central nervous system tuberculomas seen on positive SPECT in a patient with AIDS and multiresistant tuberculosis].
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AIDS-Related Opportunistic Infections↗
Biomedical subjects
K Miller
Publications and source records attributed to K Miller.
Relief of sore throat with the anti-inflammatory throat lozenge flurbiprofen 8.75 mg: a randomised, double-blind, placebo-controlled study of efficacy and safety.
In this double-blind study, 301 patients with subjective and objective signs of sore throat were randomly assigned to flurbiprofen 8.75 mg (n = 129), flurbiprofen 12.5 mg (n = 43) or placebo (demulcent lozenge without active drug [n = 129]). Efficacy was assessed by changes in subjective rating scales primarily after a single dose and also over a 4-day period. Flurbiprofen 8.75 mg was superior to placebo in a number of efficacy parameters, notably throat soreness. Throat soreness was significantly reduced after 15 minutes (p < 0.05), with effects sustained for at least 2 hours (p < 0.05). Multiple dosing with flurbiprofen 8.75 mg lozenges continued to provide effective symptomatic relief over the 4-day treatment period. The small sample size was considered contributory to the variable results obtained with flurbiprofen 12.5 mg lozenges, but overall these were not inconsistent with previous trials. Both treatments were tolerated well. Flurbiprofen 8.75 mg lozenges provide an effective and well tolerated treatment for sore throat.
Adolescent↗
Clinical utility of blood cultures drawn from indwelling central venous catheters in hospitalized patients with cancer.
BACKGROUND: Because of concern about low specificity, the American College of Physicians guidelines and expert opinion discourage the use of a central venous catheter when obtaining blood for culture for bacteremia or fungemia. However, data on the reliability of cultures done with blood obtained from a central venous catheter are conflicting. OBJECTIVE: To determine the sensitivity, specificity, and positive and negative predictive values of cultures done with blood obtained through a central venous catheter compared with peripheral venipuncture. DESIGN: Retrospective cohort study of hospitalized patients with cancer in whom samples for paired cultures were drawn through a central venous catheter and peripheral venipuncture. SETTING: Tertiary care, university-affiliated medical center. PATIENTS: 185 patients hospitalized on a hematology-oncology ward between August 1994 and June 1996. MEASUREMENTS: Blinded assessments of culture results done by infectious disease experts were used as the gold standard. Sensitivity, specificity, and positive and negative predictive values were compared for culture of blood from central catheters and culture of blood from peripheral venipuncture. RESULTS: Of 551 paired cultures, 469 (85%) were catheter-negative/venipuncture-negative, 32 (6%) were catheter-positive/venipuncture-positive, 17 (3%) were catheter-negative/venipuncture-positive, and 33 (6%) were catheter-positive/venipuncture-negative pairs. For the 82 paired cultures with at least one positive result, blinded determination of true bacteremia or fungemia was made by two infectious disease specialists. For catheter draw compared with peripheral venipuncture, sensitivity was 89% (95% CI, 79% to 98%) and 78% (CI, 65% to 90%) (difference, 11 percentage points [CI, -6 to 28 percentage points]), specificity was 95% (CI, 93% to 97%) and 97% (CI, 96% to 99%) (difference, -2 percentage points [CI, -5 to 0.2 percentage points]), positive predictive value was 63% (CI, 50% to 75%) and 73% (CI, 60% to 86%) (difference, -10 percentage points [CI, -26 to 5 percentage points]), and negative predictive value was 99% [CI, 97% to 100%]) and 98% (CI, 96% to 100%) (difference, 1 percentage point [CI, -0.5 to 3 percentage points]). CONCLUSIONS: In hospitalized hematology-oncology patients, culture of blood drawn through either the central catheter or peripheral vein shows excellent negative predictive value. Culture of blood drawn through an indwelling central venous catheter has low positive predictive value, apparently less than from a peripheral venipuncture. Therefore, a positive result from a catheter needs clinical interpretation and may require confirmation. However, the use of a catheter to obtain blood for culture may be an acceptable method for ruling out bloodstream infections.
Anti-Bacterial Agents↗
Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis.
OBJECTIVE: To 1) compare monthly serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-type 1 (TIMP-1) in patients with relapsing-remitting MS (RRMS) versus healthy controls and 2) determine the relationship among monthly serum levels of MMP-9 and TIMP-1 and MRI activity. BACKGROUND: Activated T-cells and macrophages secrete MMPs that may facilitate their migration across vascular subendothelial basement membranes into the CNS. The serum concentration of MMP-9 is reported to be higher in patients with RRMS than healthy controls. METHODS: Monthly evaluations including gadolinium-enhanced (Gd+) brain MRI and measures of serum MMP-9 and TIMP-1 were performed for up to 15 months in 24 patients with RRMS and for up to 4 months in 10 controls. RESULTS: Serum MMP-9 but not TIMP-1 levels are elevated in RRMS patients compared to healthy controls (p = 0.025, p = 0.61). In a univariate analysis, high MMP-9 and low TIMP-1 levels precede appearance of new Gd+ lesions (respectively; odds ratio = 3.3, p = 0.008; odds ratio = 2.2, p = 0.086). In a multivariate analysis, in comparison to months when MMP-9 is low and TIMP-1 high, MRI scans obtained the month following high MMP-9 and low TIMP-1 serum concentrations are more likely to report new Gd+ lesions (p = 0.0006, odds ratio = 21.5). CONCLUSION: An increase in the activity of matrix metalloproteinase-9 (MMP-9) relative to tissue inhibitor of MMP-type 1 (TIMP-1) may be related to formation of new MS lesions, suggesting that serum levels of MMP-9 and TIMP-1 may be surrogate markers of disease activity in relapsing-remitting MS.
Adolescent↗
Identification of multiple Gypsy LTR-retrotransposon lineages in vertebrate genomes.
Gypsy LTR-retrotransposons have been identified in the genomes of many organisms, but only a small number of vertebrate examples have been reported to date. Here we show that members of this family are likely to be widespread in many vertebrate classes with the possible exceptions of mammals and birds. Phylogenetic analyses demonstrate that although there are several distinct lineages of vertebrate gypsy LTR-retrotransposons, the majority clusters into one monophyletic clade. Groups of fungal, plant, and insect elements were also observed, suggesting horizontal transfer between phyla may be infrequent. However, in contrast to this, there was little evidence to support sister relationships between elements derived from vertebrate and insect hosts. In fact, the majority of the vertebrate elements appeared to be most closely related to a group of gypsy LTR-retrotransposons present within fungi. This implies either that at least one horizontal transmission between these two phyla has occurred previously or that a gypsy LTR-retrotransposon lineage has been lost from insect taxa.
Animals↗
[Lymph node positive prostate carcinoma. A case for radiotherapy].
The role of radiotherapy of the pelvic lymphatic pathways in patients with node positive prostate cancer remains uncertain. Interpretation of the few prospective studies (RTOG 75-06 and 77-06) is hampered by severe flaws in the study design. Extension of the radiation to the paraaortal region shows no advantage over radiation of the pelvic lymphatics alone and is not warranted. Data on longterm side-effects are only available from older studies with outdated radiation techniques. According to more recent studies short term side effects are considerably higher with radiation of the pelvic lymphatics when compared with radiation of the prostate alone. In summary radiation of the lymphatic pathways in lymph node positive prostate cancer cannot currently be considered as standard treatment and should be carried out within clinical studies.
Clinical Trials as Topic↗
Constitutive model of brain tissue suitable for finite element analysis of surgical procedures.
Realistic finite element modelling and simulation of neurosurgical procedures present a formidable challenge. Appropriate, finite deformation, constitutive model of brain tissue is a prerequisite for such development. In this paper, a large deformation, linear, viscoelastic model, suitable for direct use with commercially available finite element software packages such as ABAQUS is constructed. The proposed constitutive equation is of polynomial form with time-dependent coefficients. The model requires four material constants to be identified. The material constants were evaluated based on unconfined compression experiment results. The analytical as well as numerical solutions to the unconfined compression problem are presented. The agreement between the proposed theoretical model and the experiment is good for compression levels reaching 30% and for loading velocities varying over five orders of magnitude. The numerical solution using the finite element method matched the analytical solution very closely.
Algorithms↗
Randomized trial of peripheral blood progenitor cell vs bone marrow as hematopoietic support for high-dose chemotherapy in patients with non-Hodgkin's lymphoma and Hodgkin's disease: a clinical and molecular analysis.
Filgrastim (r-metHuG-CSF)-mobilized peripheral blood progenitor cells (PBPC) and unstimulated bone marrow (BM) were evaluated and compared for reconstitution after high-dose chemotherapy in patients with relapsed Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) with respect to engraftment, overall and relapse-free survival, and contamination by lymphoma cells using molecular analysis of immunoglobulin gene rearrangements. Forty-four patients with either NHL or HD underwent autologous transplantation after high-dose chemotherapy. Patients were randomized to receive either Filgrastim-mobilized PBPC (n = 15) or unstimulated BM (n = 14). An additional 15 patients received PBPC without randomization because of a recent history of marrow involvement by lymphoma. Use of PBPC was associated with faster neutrophil engraftment than BM (11 vs 14 days to an absolute neutrophil count >0.5 x 10(9)/l, P = 0.04), but without any difference in platelet engraftment, infectious complications, or overall or event-free survival. Both BM (65%) and PBPC (73%) were frequently contaminated by tumor cells as assessed by CDR3 analysis. Patients with negative polymerase chain reaction analysis of a BM sample during the study had a trend towards an improved survival; however, BM involvement by disease had no impact on the ability to mobilize or collect PBPC. We conclude that PBPC are as effective as BM in reconstituting hematopoiesis after high-dose chemotherapy and that both products are frequently contaminated by sequences marking the malignant clone.
Adult↗
Allergy to bovine beta-lactoglobulin: specificity of immunoglobulin E generated in the Brown Norway rat to tryptic and synthetic peptides.
BACKGROUND: Animal models which reflect the induction and development of food-allergic reactions are important in the identification of allergenic potential of food proteins and peptides. A number of rat strains, including PVG, Hooded Lister and Brown Norway have been shown to produce immunoglobulin (Ig) E antibodies to food proteins as well as to inhaled allergens. Previous work in our laboratory using the Brown Norway (BN) rat has shown that specific IgE is produced following administration of ovalbumin and milk products via both enteral and parenteral route; this has allowed us to rank ovalbumin, lactoferrin and bovine serum albumin in terms of their inherent allergenic potential and has enabled us to demonstrate that milk protein allergens recognized by the systemically-sensitized animal are consistent with those recognized by sera from cow's milk-allergic patients (the most common allergens recognized were beta-lactoglobulin and the alpha, beta and kappa-caseins). OBJECTIVE: To demonstrate that the BN rat model can be used to identify the major IgE-binding peptides from beta-lactoglobulin, a known human food allergen, and that those IgE-binding peptides are similar to those recently identified using sera from cow's milk-allergic patients. METHODS: BN rats were exposed to beta-lactoglobulin or to semiskimmed milk via the intraperitoneal route in the presence of the adjuvant carrageenan. Specific IgE raised against beta-lactoglobulin was determined by a direct enzyme immunoassay using acetyl-cholinesterase substrate; specific IgG responses were also monitored. Overlapping synthetic peptides and tryptic peptides were used within the ELISA to identify the major and minor IgE-binding immunoreactive sequences. RESULTS: In terms of comparative immunogenicity, there appeared to be sequences that were predominantly IgE- or IgG-reactive. IgE-dominant regions were amino acid sequences 21-40, 41-60, 107-117 and 148-168 whereas sequences 1-24, 67-77, 82-92, 85-95 and 117-127 appeared more selective for IgG antibody recognition. An increased capacity to induce specific IgE was observed when the allergen was present in the context of whole food. CONCLUSIONS: These studies provide evidence that the immune system of the BN rat and humans - at least in the case of milk allergens - is recognizing similar protein allergens and indeed, at the molecular level, similar peptide epitopes.
Animals↗
Long-term survival after surgery for recurrent advanced sarcomatoid renal carcinoma.
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Aged↗
Serum gelatinase B, TIMP-1 and TIMP-2 levels in multiple sclerosis. A longitudinal clinical and MRI study.
Metalloproteinases have been implicated in the pathogenesis of multiple sclerosis. We report longitudinal serum levels of gelatinase B and of the tissue inhibitors of matrix metalloproteinases (TIMP), TIMP-1 and TIMP-2, in 21 patients with relapsing multiple sclerosis. Patients had monthly clinical and gadolinium-enhanced MRI follow-up for 10 months. Longitudinal samples in nine healthy controls and cross-sectional samples from 12 patients with inflammatory CNS disease and 15 patients with other neurological diseases were used for comparison. Average serum gelatinase B, TIMP-1 and TIMP-2 levels were significantly higher in multiple sclerosis patients and those with other neurological diseases than in healthy controls. In the patients with multiple sclerosis, gelatinase B levels were significantly higher during clinical relapse compared with periods of clinical stability. Multiple sclerosis patients with high mean serum gelatinase B levels had significantly more T1-weighted gadolinium-enhancing MRI lesions than those with mean levels within the control range. TIMP-1 levels were not different during relapse and between relapses. There was a trend for TIMP-2 levels to be lower during relapse compared with non-relapse periods. For similar levels of serum gelatinase B, associated TIMP-1 levels were significantly lower and TIMP-2 levels significantly higher in multiple sclerosis patients compared with the inflammatory CNS control group. We propose that an abnormality in the inhibitory response to metalloproteinases may play an aetiological role in the chronicity of multiple sclerosis.
Adult↗
Professional growth through volunteerism.
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Aged↗
A biophenotypic human herpesvirus 8--associated primary bowel lymphoma.
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Adult↗
Urothelial carcinoma in a suprapubic cystostomy tract 27 years after tube removal.
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Carcinoma, Transitional Cell↗
Screening inpatient quality using post-discharge events.
BACKGROUND: Decreasing hospital lengths of stay (LOS) hamper efforts to detect and to definitively treat complications of care. Patients leave before some complications are identified. OBJECTIVES: To develop a computerized method to screen for hospital complications using readily available administrative data from outpatient and nonacute care within 90 days of discharge. DESIGN: We developed the Complications Screening Program for Outpatient data (CSP-O) by using diagnosis and procedure codes from Medicare Part A and B claims to define 50 complication screens. Seventeen apply to specific procedural cases, and 33 apply to all adult, acute, medical, or surgical hospitalizations. The CSP-O algorithm examined outpatient, physician office, home health agency, and hospice claims within 90 days following discharge. SUBJECTS: Seven hundred thirty nine thousand, two hundred and forty eight discharges of Medicare beneficiaries (age range, > or = 65 years) were admitted to 515 hospitals nationwide in 1994. RESULTS: Complete 90-day, post-discharge windows were present for 62.8% of all and 68.5% of procedural cases. The 33 general screens flagged 13.6% of all cases; only 1.8% of procedural cases were flagged by the 17 procedural screens. When we allowed the CSP-O algorithm to scan information from acute hospital readmissions, flag rates rose to 32.8% for general and 8.7% for procedural complications. Controlling for patient and hospital characteristics, flag rates were considerably higher among the very old and at small and for-profit institutions. CONCLUSIONS: Whereas several CSP-O findings have construct validity, limitations of claims raise concerns. Regardless of the CSPO's ultimate utility, examining post-discharge experiences to identify inpatient complications remains important as LOSs fall.
Aftercare↗
Use of alcohol fixed cytospins protected by 10% polyethylene glycol in immunocytology external quality assurance.
AIMS: To provide cytospins as a means of external quality assurance (EQA), while maintaining antigen expression integrity and achieving uniformity of material for all participating laboratories. METHODS: Cells were collected from two adenocarcinoma and one reactive pleural effusion specimens. Lymphoid cells were also collected through aspiration of a resected tonsil specimen. All cells were collected in Hanks balanced salt solution (HBSS); cytospins were made and fixed in methanol or acetone alone or protected using a layer of 10% polyethylene glycol (PEG) in 50% methanol. Two laboratories participated (RGHT and UCL). RESULTS: Cytokeratin expression detected using either CAM5.2 or AE1/AE3 antibodies was sensitive to temperature. Without PEG, unacceptable or negative staining was seen within six weeks of preparation. LCA was not sensitive to temperature, with good staining scores being achieved after eight weeks following preparation. CONCLUSIONS: It is possible to send alcohol fixed, air dried cytospins to laboratories participating as part of an EQA scheme for immunocytology. Some antigens will require protection from temperature variations during transit. A layer of 10% PEG in 50% methanol, allowed to air dry, is suitable for this purpose. Participating laboratories will only have to remove this layer using methanol before their localisation technique for assessment.
Adenocarcinoma↗
Quantitative detection of human complement factor H-related protein in transitional cell carcinoma of the urinary bladder.
OBJECTIVE: The purpose of this study was to assess a new quantitative urinary tumor marker for transitional cell carcinoma of the urinary bladder (TCC), human complement factor H-related protein (hCFHrp, BTA TRAK). METHODS: Urine samples of 298 individuals (76 healthy volunteers, 118 patients with benign urologic disorders, 104 patients with histologically proven bladder cancer) were examined for the presence of hCFHrp. Samples of all patients were obtained prior to therapy. RESULTS: In comparison to healthy volunteers, patients with TCC had significantly higher urinary levels of hCFHrp (117.60 vs. 2.05 U/ml; p < 0.001). HCFHrp levels were positively correlated with tumor grade and stage. Patients with invasive TCC had significantly higher levels of hCFHrp than patients with superficial TCC (p = 0.001). Marker levels in superficial bladder cancer at high risk of tumor progression (pT1G3) were significantly higher as compared to low and intermediate grade superficial cancers. Elevated levels of hCFHrp were also found in patients with benign urologic disorders (median: 72.65 vs. 117.60 U/ml in cancer patients). Using a cutoff of 17.1 U/ml, hCFHrp had a sensitivity of 72.1% and, due to a high rate of false-positive determinations in patients with benign urologic disorders, a total specificity of 50.5%. CONCLUSIONS: HCFHrp (BTA TRAK) is a sensitive test for detection of bladder cancer and for identification of patients at high risk. Due to a high rate of false-positive results in patients with benign urologic diseases, the test should not be used in an unselected population.
Adult↗
Telomerase activity in malignant and benign renal tumors.
OBJECTIVES: An important characteristic of malignant cells is their unlimited replicative potential, their immortality. In conferring this immortality, the enzyme telomerase is believed to play a crucial role. The detection of telomerase activity provides new knowledge regarding the biologic growth behavior of tumors and offers new diagnostic and therapeutic tools. METHODS: In the present study the sensitive TRAP assay (telomeric repeat amplification protocol) was used to examine 44 malignant renal tumors and 8 benign tumors of the kidney and 52 specimens of normal renal tissue for telomerase activity. RESULTS: Telomerase activity was detected in 63% of tissue samples obtained from histologically confirmed renal cell carcinomas. In cases of renal cell carcinoma restricted to the kidney, telomerase activity was detected in 58%. In cases in which tumor growth has progressed beyond the limits of the organ, telomerase activity was found in 69%. This stage dependence, however, did not reach statistical significance. No correlation to tumor grading was observed. Telomerase activity was found less frequent in chromophobe renal cell carcinomas. Neither the 8 benign renal tumors (4 oncocytomas and 4 angiomyolipomas) nor the specimens of normal kidney showed any evidence of telomerase activity. CONCLUSIONS: The proportion of remarkable slow-growing renal cell carcinomas showing telomerase activity is less than in other malignancies and may correlate with biologic growth behavior. Possible explanations include the presence of an alternative pathway, called ALT (alternative lengthening of telomeres) and an association with the loss or presence of the telomerase suppressor on the short arm of chromosome 3. Prolonged follow-up will be of special interest to determine whether lack of telomerase activity predicts favorable outcome.
Adenoma, Oxyphilic↗