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Biomedical subjects

D J Weber

Publications and source records attributed to D J Weber.

At least 163 records · Page 9Linked to original sources

Clinical significance of Bacillus species isolated from blood cultures.

To determine the clinical significance of blood isolates of Bacillus, we reviewed all blood cultures obtained at North Carolina Memorial Hospital between 1981 and 1985. Over the five-year study period the number of patients (incidence per 10,000 hospital admissions) from whom Bacillus was isolated increased from 4.97 in 1981 to 12.5 in 1985. The incidence per 1,000 blood cultures also increased from 1.12 in 1981 to 2.33 in 1985. Review of the medical records of 78 of the 95 patients (82%) with positive cultures allowed retrospective classification of five isolates (6.4%) as clinically significant, 33 isolates (42.3%) as possibly significant, and 40 isolates (51.3%) as nonsignificant. Underlying diseases in patients with clinically significant Bacillus bacteremia included burn trauma in two, leukemia in one, carcinoma in one, and gastrointestinal hemorrhage in one. All isolates judged to be clinically significant and the majority of possibly significant isolates were B cereus. We conclude that the isolation of Bacillus species from blood cultures is clinically significant in 5% to 10% of cases, that the incidence of Bacillus bacteremia is increasing, and that burn trauma should be added to the list of conditions known to predispose to clinically significant Bacillus bacteremia.

Adolescent↗

Epidemiology of tuberculosis in North Carolina, 1966 to 1986: analysis of demographic features, geographic variation, AIDS, migrant workers, and site of infection.

We analyzed all cases of tuberculosis reported in North Carolina between 1966 and 1986, and related the incidence rate of tuberculosis (per 100,000 population) to age (0 to 4 years, 7.59; 5 to 14 years, 3.44; 15 to 24 years, 6.30; 25 to 44 years, 15.92; 45 to 64 years, 33.85; greater than 65 years, 51.54), race (white 9.03, nonwhite 47.40), and gender (male 25.49, female 11.25). Over the 21-year study period the annual number of cases declined from 1,248 to 711 (43%), and the incidence rate from 25.56 to 11.25 (56%). Although the incidence rate of tuberculosis fell for all subgroups, nonwhites continued to have an incidence rate 3.2 to 22.5 times higher than whites, depending on age. The standardized morbidity ratio (SMR) (by age, race, and gender) of tuberculosis in the eastern region of North Carolina was nearly twice that of the western region and unexplainable by its demographics. Between 1983 and 1986 only a small percentage of cases of tuberculosis in North Carolina were accounted for by migrant farm workers (1.7% to 2.7%) and patients with the acquired immunodeficiency syndrome (less than 1%). Tuberculosis is increasingly a disease of the elderly, especially nonwhite men. Tuberculosis is a geographically and demographically focal disease in North Carolina, and preventive strategies should be appropriately targeted.

Acquired Immunodeficiency Syndrome↗

Gas chromatographic determination of guanadrel in plasma and urine.

To evaluate the pharmacokinetics and drug availability from various dosage formulations, a method for the determination of guanadrel, (1,4-dioxaspiro[4,5]dec-2-ylmethyl)guanidine, in plasma and urine was required. A gas chromatographic procedure, based on formation of a hexafluoroacetylacetone derivative in a two-phase system of water and toluene, was developed. The limit of determination of the method is 5 ng/ml guanadrel in plasma and 15 ng/ml guanadrel in urine. Statistical analyses indicate average recoveries of 98.1 +/- 18.0 and 104.4 +/- 15.6% from plasma and urine, respectively. Mass spectrometric analyses, in conjunction with gas chromatography, confirmed the specificity of the method for intact drug. The procedure was applied successfully to drug absorption studies in humans.

Chemical Phenomena↗

Phospholipid binding properties of bovine prothrombin peptide residues 1-45.

The present study investigates the unique contribution of the NH2-terminal 33 residues of prothrombin, the gamma-carboxyglutamic acid (Gla) domain, to the Ca(II) and phospholipid-binding properties of prothrombin. Two Gla domain peptides, 1-42 and 1-45, produced by chymotryptic cleavage of prothrombin fragment 1 (residues 1-156 of the amino terminus of bovine prothrombin) and isolated by anion-exchange chromatography were utilized to characterize the Gla domain of prothrombin. This investigation utilized several experimental approaches to examine the properties of the Gla domain peptides. These studies were somewhat hampered by the metal ion-induced insolubility of the peptides. However, the 1-45 peptide was specifically radioiodinated, which facilitated the study of this peptide at low concentrations. In contrast to prothrombin fragment 1, the intrinsic fluorescence of both 1-42 and 1-45 was not quenched upon the addition of 1 mM Ca(II) or any concentration of Mg(II). Equilibrium dialysis studies revealed that the 1-42 peptide bound three Ca(II) ions noncooperatively, whereas fragment 1 binds seven Ca(II) ions in a positive cooperative manner. Ca(II)-promoted conformational changes are observed by comparison of electrophoretic mobility changes in the presence of increasing Ca(II) concentrations. Prothrombin, fragment 1, and the Gla domain peptides 1-42 and 1-45 exhibited similar electrophoretic mobility behavior in the presence of Ca(II) ions. The radiolabeled 1-45 peptide was found to comigrate with phospholipid vesicles on gel permeation chromatography in the presence of Ca(II). Fragment 1 was shown to inhibit this Ca(II)-dependent phospholipid binding of 1-45, demonstrating that the 1-45 peptide does possess the necessary phospholipid-binding structure. Furthermore, a metal ion-dependent conformational monoclonal antibody, F9.29, was inhibited from binding fragment 1 by the 1-42 peptide.

Amino Acid Sequence↗

The determination of a calcium-dependent binding constant of the bovine prothrombin Gla domain (residues 1-45) to phospholipid vesicles.

Calcium-mediated binding of the radioiodinated peptide representing residues 1-45 of bovine prothrombin to single bilayer phospholipid vesicles composed of phosphatidylserine from bovine brain and synthetic 1-palmitoyl-2-oleoyl-phosphatidylcholine (25:75 PS/PC) has been studied over peptide concentrations from 0.33 microM to 3.75 microM and at a calcium concentration of 1.0 mM. The binding isotherm for the interaction between the radioiodinated peptide and PS/PC vesicles fits a model in which there is noncooperative binding of the peptide to non-interacting sites on the phospholipid bilayer. A dissociation constant determined at these conditions is 11.8 microM compared to 1.0 microM for prothrombin fragment 1.

1-Carboxyglutamic Acid↗

In vitro susceptibility of Bacillus spp. to selected antimicrobial agents.

Although often dismissed as contaminants when isolated from blood cultures, Bacillus spp. are increasingly recognized as capable of causing serious systemic infections. As part of a clinical-microbiological study, 89 strains of Bacillus spp. isolated from clinical blood cultures between 1981 and 1985 had their species determined and were tested for antimicrobial agent susceptibility to 18 antibiotics. Species of isolates were determined by the API 50CH and API 20E systems. Bacillus cereus (54 strains) was the most common species isolated, followed by B. megaterium (13 strains), B. polymyxa (5 strains), B. pumilus (4 strains), B. subtilis (4 strains), B. circulans (3 strains), B. amyloliquefaciens (2 strains), B. licheniformis (1 strain), and Bacillus spp. (3 strains). Microdilution MIC susceptibility tests revealed all B. cereus strains to be susceptible to imipenem, vancomycin, chloramphenicol, gentamicin, and ciprofloxacin. Non-B. cereus strains were most susceptible to imipenem, vancomycin, LY146032, and ciprofloxacin. Disk susceptibility testing suggested that B. cereus was rarely susceptible to penicillins, semisynthetic penicillins, or cephalosporins with the exception of mezlocillin. In contrast, many non-B. cereus strains were susceptible to penicillins, semisynthetic penicillins, and cephalosporins, but marked variability was noted among species.

Anti-Bacterial Agents↗

Impact and costs of varicella prevention in a university hospital.

Information regarding all patient and staff exposures to varicella-zoster virus (VZV) was prospectively accumulated from 1/1/86 to 12/31/86 at North Carolina Memorial Hospital. During this period of time 37 sources of exposure to VZV were reported: 10 outside and 27 within the hospital. Index cases for nosocomial exposure included: 12 patients with zoster, 9 patients with varicella, two staff with varicella, three visitors with varicella, and one staff with zoster. One hundred and twenty patients received nosocomial exposures; 28 had no history of VZV infection (23 per cent), of whom 11 were serosusceptible (39 per cent). Sources of nosocomial patient exposure included: other patients (85 per cent), staff (14 per cent), and a single visitor (1 per cent). More than 300 employees received nosocomial exposure; 158 had no history of VZV infection, of whom 49 were serosusceptible (31 per cent). Only a single employee and no patients developed clinical varicella as a result of nosocomial exposure. Costs associated with VZV control during 1986 totaled $55,934: $39,658 for work furloughs, $9,800 for serologies, $4,293 for patient isolation, $155 for varicella-zoster immune globulin, and $2,028 for infection control personnel time. These costs should be considered as part of any benefit-cost analysis of varicella immunization of health care personnel.

Chickenpox↗

An outbreak of Pseudomonas cepacia bacteremia associated with a contaminated intra-aortic balloon pump.

In January 1983, symptomatic Pseudomonas cepacia bacteremia developed in two patients in the cardiothoracic intensive care unit within 3 days after cardiac operation and insertion of an intra-aortic balloon pump. An epidemiologic and microbiologic investigation revealed that both patients required intra-aortic balloon pumping for circulatory support and that the water reservoir of the intra-aortic balloon pump (SMEC, Inc., Cookeville, Tenn.) contained more than 10(5) Pseudomonas cepacia per milliliter. This organism was also recovered from the purge button and on-off switch of the pump and from the hands of a health care worker who manipulated the water reservoir of the intra-aortic balloon pump. Agarose gel electrophoresis of lysates of Pseudomonas cepacia with rapid methods of deoxyribonucleic acid preparation revealed three identical plasmids of the Pseudomonas cepacia from the water reservoir of the intra-aortic balloon pump and from the infected patients. Transmission from the worker's hands to patients presumably occurred by inoculation of the intravascular lines during management. No additional cases of Pseudomonas cepacia bacteremia were observed after the unit was replaced with a nonwater reservior intra-aortic balloon pump. This report substantiates the ability of Pseudomonas cepacia to multiply in water and to cause epidemic bacteremia, identifies the water reservoir of the SMEC intra-aortic balloon pump as a previously unrecognized hazard for the patient requiring intra-aortic balloon pumping, and documents the value of plasmid analysis in elucidating the mode of transmission of nosocomial Pseudomonas cepacia infections.

Aged↗

High-performance liquid chromatographic determination of methylprednisolone and methylprednisolone 21-[8-[methyl-(2-sulfoethyl)amino]-8-oxoctanoate] sodium salt in human plasma.

A high-performance liquid chromatographic assay method with ultraviolet detection at 243 nm has been developed for the quantitative determination of methylprednisolone (MP) and methylprednisolone 21-[8- [methyl-(2-sulfoethyl)amino]-8-oxoctanoate] sodium salt (MPSO) in human plasma. The method is simple, rapid and sensitive to detect MP and MPSO in human plasma following administration of therapeutic doses of MPSO. The assay procedure involved stabilization of plasma samples by addition of disodium ethylenediaminetetraacetic acid and ion-pair extractions of MPSO with tetraethylammonium chloride. After extracting both drugs and internal standard into chloroform, the extract was evaporated to dryness under nitrogen. The resulting residue was reconstituted in 200-500 microliter of mobile phase and chromatographed on a C18 IBM reversed-phase column (5 micron). The mobile phase was a mixture of water-actetonitrile-isopropanol (71:19.9:10) containing 50 microliter of 0.1 M hydrochloric acid and 0.497 g tetraethylammonium chloride. Propyl p-hydroxybenzoate was used as an internal standard. The chromatographic responses were linear up to about 200 micrograms/ml for MP and 80 micrograms/ml for MPSO in human plasma. The assay detection limit was approximately 7 ng/ml for MP and 25 ng/ml for MPSO in human plasma. Statistical analysis indicated an average recovery of 102.0 +/- 4.71% for MP and 75.2 +/- 2.88% for MPSO. Human plasma levels are reported for MP and MPSO following single-dose intravenous administration of 100-mg equivalents of MPSO.

Adolescent↗

Ampicillin versus cefamandole as initial therapy for community-acquired pneumonia.

One hundred seven patients with community-acquired pneumonia thought to be of bacterial etiology by the admitting physician but whose initial sputum Gram stain was inadequate to direct specific therapy were randomized to receive either intravenous ampicillin or cefamandole as empiric therapy. Patients were excluded if the initial sputum Gram stain was highly suggestive of infection with Streptococcus pneumoniae, Staphylococcus aureus, or an enteric gram-negative bacillus. The two study groups had comparable demographic and presenting clinical features. The mean age of the patients evaluable for determination of clinical efficacy was 69 years, and greater than 75% had at least one serious underlying medical disorder. In the 90 evaluable patients, there were 11 therapeutic failures (12%), including 5 deaths (5%). Cefamandole, a broad-spectrum antibiotic, was not more efficacious than ampicillin in producing a satisfactory clinical response or in shortening the duration of parenteral therapy. Patients received an average of only 4 days of intravenous antibiotics before changeover to oral therapy and were hospitalized for a mean of 7 days. No patient experienced a relapse of pneumonia following successful completion of parenteral drug therapy. We conclude that cefamandole is not a more effective agent than ampicillin for empiric therapy of community-acquired bacterial pneumonia of uncertain etiology.

Administration, Oral↗

Outbreak of wound infections following outpatient podiatric surgery due to contaminated bone drills.

An outbreak of podiatric infections due to an uncommon strain of Proteus mirabilis occurred following outpatient podiatric surgery. An evaluation of the operating room environment failed to reveal the strain of P. mirabilis from any site other than three bone drills. Thus the drills served as the reservoir for the organism that was subsequently inoculated onto the hands of the surgeon or directly to a patient during bone drilling. The gas sterilization procedure that was used to sterilize the drills was found deficient. No additional cases of P. mirabilis infection have been observed since the elimination of the contaminated drills.

Adult↗

Acquired immunodeficiency syndrome: epidemiology and significance for the obstetrician and gynecologist.

A retrovirus, variously named human T-lymphotropic virus type III or lymphadenopathy-associated virus, is now recognized as the etiologic agent of the acquired immunodeficiency syndrome. As of January, 1986, more than 16,000 cases of acquired immunodeficiency syndrome have been reported, and it is estimated that greater than or equal to 1 million Americans are now infected with human T-cell lymphotropic virus/lymphadenopathy-associated virus. Most cases of overt acquired immunodeficiency syndrome still fall within well-defined "high-risk groups," that is, homosexual or bisexual men, intravenous drug users, recipients of transfused blood or blood components, and persons with hemophilia. Also at risk are heterosexual partners of persons who have overt acquired immunodeficiency syndrome or who are at risk for acquired immunodeficiency syndrome, as are children born to mothers who either have acquired immunodeficiency syndrome or are members of a "high-risk group." Transmission of the virus may occur via sexual contact, via parenteral exposure to contaminated blood products, or from an infected mother to her child. Of special concern to the practicing obstetrician are recent reports suggesting bidirectional heterosexual transmission, transmission via artificial insemination, and perinatal transmission. In addition, the isolation of human T-cell lymphotropic virus/lymphadenopathy-associated virus from human breast milk raises concerns regarding potential transmission by this route.

Acquired Immunodeficiency Syndrome↗

Obesity as a predictor of poor antibody response to hepatitis B plasma vaccine.

Factors associated with lack of antibody response to the hepatitis B virus plasma vaccine were retrospectively evaluated by means of a logistic regression in 194 previously seronegative staff members of a community hospital. All subjects had received three doses of vaccine by intramuscular buttock injection using a 1-in, 23-gauge needle. Overall, only 55.7% of subjects developed detectable antibody to hepatitis B surface antigen in serum after immunization. The weight-height index served as a surrogate measure of obesity. Predictors of poor immunogenic response to hepatitis B vaccine included higher weight-height index, older age, and vaccine batch. Sex, race, timing of vaccine doses, and timing of postimmunization determination of antibody to hepatitis B surface antigen were not predictors of vaccine efficacy.

Adult↗