The pharmacokinetics and protein-binding of fusidic acid in patients with severe renal failure requiring either haemodialysis or continuous ambulatory peritoneal dialysis

Antibiotic treatment options for Burkholderia cepacia infection are limited because of high intrinsic resistance. The problem is complicated by development of cross-resistance between antibiotics of different classes. We isolated antibiotic-resistant mutants by stepwise exposure to chloramphenicol (Chlor) and to trimethoprim/sulphamethoxazole (T/S) for four B. cepacia strains: ATCC13945, Per (clinical isolate), Cas and D4 (environmental isolates). Chlor(r) mutants did not produce chloramphenicol acetyl-transferase. Cross-resistance, defined as greater than four-fold increase in MIC by microtitre dilution method, was consistently seen in both types of mutants. For chloramphenicol-resistant (Chlor[r]) and trimethoprim/sulphamethoxazole-resistant (Tr/Sr) mutants of B. cepacia ATCC13945 and Cas, no MIC change was seen for piperacillin, ceftazidime, rifampicin, gentamicin, tobramycin, polymyxin B or azithromycin. B. cepacia-Per and -D4 mutants showed cross-resistance to ceftazidime and to piperacillin. Comparison of outer membrane protein (OMP) profiles of B. cepacia and their mutants by SDS-PAGE revealed Tr/Sr) mutants to be deficient in a major OMP (molecular weight 39-47 kDa). Tr/Sr mutants also expressed additional OMPs not found in wild type strains at 75-77 kDa for B. cepacia-ATCC13945 and -Cas, and 20-21 kDa in B. cepacia-D4 and -Per. No OMP changes occurred in Chlor(r) mutants. Lipopolysaccharide (LPS) profiles of each type of mutant showed new high and low molecular weight LPS bands. Cross-resistance seems to be mediated by alterations in porin and LPS for Tr/Sr mutants, but only by LPS in Chlor(r) mutants.     

Context-specific adaptation of vertical vergence to correlates of eye position

Vertical phoria (vertical vergence in the absence of binocular feedback) can be trained to vary with non-visual cues such as vertical conjugate eye position, horizontal conjugate eye position and horizontal vergence. These prior studies demonstrated a low-level association or coupling between vertical vergence and several oculomotor cues. As a test of the potential independence of multiple eye-position cues for vertical vergence, context-specific adaptation experiments were conducted in three orthogonal adapting planes (midsagittal, frontoparallel, and transverse). Four vertical disparities in each of these planes were associated with various combinations of two specific components of eye position. Vertical disparities in the plane were associated with horizontal vergence and vertical conjugate eye position; vertical disparities in the frontoparallel plane were associated with horizontal and vertical conjugate eye position; and vertical disparities in the transverse plane were associated with horizontal vergence and horizontal conjugate eye position. The results demonstrate that vertical vergence can be adapted to respond to specific combinations of two different sources of eye-position information. The results are modeled with an association matrix whose inputs are two classes of eye position and whose weighted output is vertical vergence.     

The natural killer cell receptor specific for HLA-A allotypes: a novel member of the p58/p70 family of inhibitory receptors that is characterized by three immunoglobulin-like domains and is expressed as a 140-kD disulphide-linked dimer

Human natural killer (NK) cells express inhibitory receptors that are specific for different groups of HLA-C or HLA-B alleles. The majority of these receptors belong to the immunoglobulin (Ig) superfamily and are characterized by two or three extracellular Ig-like domains. Here we describe a novel inhibitory NK receptor that is specific for a group of HLA-A alleles. The HLA-A3-specific NK cell clone DP7 has been used for mice immunization. Two mAbs, termed Q66 and Q241, bound to the immunizing clone and stained only a subset of NK cell populations or clones. Among Q66 mAb-reactive clones, we further selected those that did not express any of the previously identified HLA-class I-specific NK receptors. These clones did not lyse HLA-A3+ (or -A11+) target cells, but lysis of these targets could be detected in the presence of Q66 or Q241 mAbs. On the other hand, target cells expressing other HLA-A alleles, including -A1, -A2, and -A24, were efficiently lysed. Moreover, none of the HLA-C or HLA-B alleles that were tested exerted a protective effect. Q66+, but not Q66- NK cell clones, expressed messenger RNA coding for a novel 3 Ig domain protein homologous to the HLA-C (p58) and HLA-B (p70) receptors. The corresponding cDNA (cl.1.1) was used to generate transient and stable transfectants in COS7 and NIH3T3 cell lines, respectively. Both types of transfectants were specifically stained by Q66 and Q241 mAbs. Since the cytoplasmic tail of Q66-reactive molecules was at least 11 amino acid longer than the other known p58/p70 molecules, we could generate an antiserum specific for the COOH-terminus of Q66-reactive molecules, termed PGP-3. PGP-3 immunoprecipitated, only from Q66+ NK cells, molecules displaying a molecular mass of 140 kD, under nonreducing conditions, which resolved, under reducing conditions, in a 70-kD band. Thus, differently from the other p58/p70 receptors, Q66-reactive molecules appear to be expressed as disulphide-linked dimers and were thus termed p140. The comparative analysis of the amino acid sequences of p58, p70, and p140 molecules revealed the existence of two cysteins proximal to the transmembrane region, only in the amino acid sequence of p140 molecules.     

Incidence of Lightspeed separation and the potential for bypassing

It is important for endodontic instruments to have a low fracture rate. If a fracture does occur, it would be desirable to have the ability to bypass the broken segment and complete the root canal treatment. One hundred sixty-two root canals in 52 maxillary and mandibular first molars were cleaned and shaped with Lightspeed instruments by three endodontists in their private practices. The canals were instrumented using the technique recommended by the manufacturer. All canals were instrumented to at least a size 45 at the working length. Six instruments separated during treatment. All six had been used more times than recommended by the manufacturer. Five of the six were easily bypassed and treatment completed.     

Association of symptoms of depression with diagnostic test charges among older adults

BACKGROUND: Previous studies have documented greater use of health services by depressed persons and have postulated that health care costs could be reduced overall through better recognition and treatment of depression. OBJECTIVE: To determine whether a greater burden of medical illness contributes to excess charges for diagnostic tests among older adults with symptoms of depression. DESIGN: Prospective cohort study. SETTING: A primary care group practice at an academic institution. PATIENTS: 3767 patients 60 years of age and older who completed testing on the Centers for Epidemiologic Studies Depression Scale (CES-D) during routine office visits. MEASUREMENTS: Charges for all inpatient and ambulatory diagnostic testing for 2 years, including clinical pathology, diagnostic imaging, and special procedures; number of visits to the ambulatory care center or emergency department; and number of hospitalizations. The Ambulatory Care Group case-mix approach, which is based on ambulatory diagnoses, was used as a measure of health status and expected resource consumption. RESULTS: Patients with symptoms of depression (CES-D scores > or = 16) were significantly younger (66.6 compared with 68.1 years; P < 0.001), more likely to be white (50.5% compared with 33.9%; P = 0.001), and more likely to be female (75.8% compared with 67.6%; P = 0.001) than were those without these symptoms (CES-D scores < 16). They also had more nonpsychiatric comorbid conditions, had more visits to the ambulatory care center (9.2 compared with 7.8; P < 0.001), were more likely to use the emergency department (52.3% compared with 40%; P = 0.001), were more likely to be hospitalized (22.4% compared with 17%; P = 0.002), and had greater median total diagnostic test charges for a period of 1 year ($583 compared with $387; P < 0.001). The difference in charges, most of which were clinical pathology charges (54.2%), persisted into the second year. Ambulatory Care Group assignment was independently associated with diagnostic test charges. The CES-D summary score was not independently associated with diagnostic test charges when controlling for Ambulatory Care Group assignment. CONCLUSIONS: Patients with symptoms of depression accrue greater average diagnostic test charges. However, these data suggest that such patients also have a greater burden of comorbid nonpsychiatric illness. Efforts to improve outcome and decrease cost for patients who have late-life depression must target interventions to improve the care of psychiatric and medical illness concurrently.     

Comparison of clinical diagnosis and standard laboratory and molecular methods for the diagnosis of genital ulcer disease in Lesotho: association with human immunodeficiency virus infection

A multiplex polymerase chain reaction (M-PCR) assay for Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV) was compared with clinical and standard laboratory methods for the diagnosis of genital ulcer disease (GUD) in 105 patients; 36% were human immunodeficiency virus (HIV)-seropositive. Chancroid (80%), syphilis (8%), and genital herpes (8%) were the most frequent diagnoses. H. ducreyi and HSV were isolated from ulcers of 43% and 18% of patients, respectively; in 35%, all cultures were negative and the laboratory diagnosis indeterminate. M-PCR detected H. ducreyi, T. pallidum, and HSV in 56%, 23%, and 26% of patients, respectively; (no definitive diagnosis, 6%). The proportion of patients with more than one agent was 4% by culture and 17% by M-PCR (P = .002). Resolved sensitivities of M-PCR for H. ducreyi and HSV cultures were 95% and 93%, respectively. The sensitivities of H. ducreyi and HSV cultures were 75% and 60%, respectively. HSV, detected in 47% of specimens from HIV-infected versus 16% from HIV-uninfected patients (P < .001), may be emerging as a more frequent cause of GUD.