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W K Hadley

Publications and source records attributed to W K Hadley.

At least 55 records · Page 3Linked to original sources
PubMed1990

The role of human immunodeficiency virus infection in pneumococcal bacteremia in San Francisco residents.

Human immunodeficiency virus (HIV) is an important risk factor for invasive pneumococcal disease, but information on clinical course and infecting serotypes is limited. To help develop strategies to reduce the morbidity due to invasive pneumococcal disease, episodes of pneumococcal bacteremia were identified by retrospective review of microbiology records (November 1983-November 1987) at 10 San Francisco hospitals and, for patients 20-55 years old living in San Francisco, HIV antibody status was determined by review of medical records. Pneumococcal isolates from one hospital were serotyped. Of 294 patients with pneumococcal bacteremia identified, 32 (11%) had AIDS at the time pneumococcal bacteremia was diagnosed and another 43 (15%) were HIV-infected but did not have AIDS; 12 HIV-infected patients developed AIDS after the episode of pneumococcal bacteremia. The rate of pneumococcal bacteremia in AIDS patients was estimated to be 9.4/1000 patient-years. Serotypes of 27 (82%) of 33 pneumococcal isolates from HIV-infected patients and 107 (90%) from 119 patients without known HIV infection were among the 23 serotypes included in the currently available polysaccharide vaccine. The rate of pneumococcal bacteremia is approximately 100-fold greater in AIDS patients in San Francisco than rates reported before the AIDS epidemic, but more than half the episodes of pneumococcal bacteremia in HIV-infected patients occurred in patients without AIDS. Data on pneumococcal serotypes causing invasive disease in HIV-infected patients suggest that the current pneumococcal vaccine, if effective in this population, could provide significant protection against pneumococcal disease.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Determination of guanine-plus-cytosine content of bacterial DNA by dual-laser flow cytometry.

A dual-laser flow cytometer was used to analyse different species of bacteria for the molar percentage of guanine-plus-cytosine (% G + C) without the need for DNA extraction or purification. Ethanol-fixed bacterial cells were stained with a combination of DNA-specific fluorochromes, Hoechst 33258 and chromomycin A3, which bind to AT- and GC-rich regions of DNA, respectively. A linear relationship (r = 0.99) was demonstrated between the log of the ratio of chromomycin A3 to Hoechst 33258 fluorescence and the log of the % G + C as determined by thermal denaturation (Tm) or buoyant density centrifugation (Bd) methods. Linearity was maintained for all bacterial species tested over the range of 28-67% G + C. A standard curve was constructed using five strains whose % G + C had been determined by other methods. From the equation describing this line, the % G + C values of nine other strains with known DNA base composition, together with the five strains used to construct the curve, were calculated using the chromomycin A3 to Hoechst 33258 ratio and were in agreement with values obtained by Tm, Bd or HPLC. The reproducibility of flow cytometric analysis (mean error 0.7% G + C) compared well with the reproducibility of other methods. Mixtures containing two species were also analysed. Two cell populations could be discerned in mixtures containing two species which differed in base composition by as little as 4% G + C.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytosine↗
PubMed1990

In vitro susceptibility of Mycobacterium avium complex to the new fluoroquinolone sparfloxacin (CI-978; AT-4140) and comparison with ciprofloxacin.

We tested the activity of the new fluoroquinolone sparfloxacin (CI-978; AT 4140) against 30 strains of Mycobacterium avium complex (MAC) isolated from patients with acquired immune deficiency syndrome. MICs of sparfloxacin (range, less than or equal to 0.06 to 4 micrograms/ml) were lower than MICs of ciprofloxacin for all 30 strains, and MBCs for acid-fast bacteria were lower for 28 of the 30 strains. In synergism experiments using 10 strains of MAC, fractional inhibitory concentration indices revealed that the combination of sparfloxacin plus ethambutol was synergistic against 9 strains, and the three-drug combination of sparfloxacin plus ethambutol plus rifampin was synergistic against all strains. In the absence of ethambutol, the combination of sparfloxacin plus rifampin appeared to be antagonistic against three of the MAC strains.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Rapid detection of Pneumocystis carinii using a direct fluorescent monoclonal antibody stain.

A collaborative study was undertaken at two institutions to assess the performance of a direct fluorescent-antibody stain for the detection of Pneumocystis carinii in respiratory specimens from patients with known or suspected human immunodeficiency virus type 1 infections. A total of 163 specimens (125 induced sputa, 37 bronchoalveolar lavage fluids, and 1 tracheal aspirate) from 124 patients were examined by using modified Giemsa (Diff-Quik; Baxter American Scientific Products, Chicago, Ill.) and direct fluorescent-antibody stains. A total of 73 specimens contained P. carinii, which was detected in 66 (92%) of the specimens by using the modified Giemsa and in 71 (97%) of the specimens by using the fluorescent-antibody stain. One bronchoalveolar lavage fluid specimen in which P. carinii was detected only with the fluorescent-antibody stain was determined to be a false-positive based on subsequent clinical evaluation of the patient. Although the overall time for processing and examining specimens stained with either stain was not significantly different for those specimens containing P. carinii, considerably less time was required for microscopic examination of those fluorescent-antibody-stained specimens lacking P. carinii.

Antibodies, Monoclonal↗
PubMed1990

Campylobacter-like organisms are uncommon pathogens in patients infected with the human immunodeficiency virus.

Over a 25-month period, we prospectively evaluated 36 patients with symptomatic human immunodeficiency virus disease (including 27 with unexplained chronic diarrhea) by flexible sigmoidoscopy for the presence of Campylobacter-like organisms. No Campylobacter-like organisms were isolated. Campylobacter-like organisms appear to be an uncommon cause of idiopathic chronic diarrhea in symptomatic human immunodeficiency virus disease.

Campylobacter↗
PubMed1989

Comparative recovery of cytomegalovirus from saliva, mucolysed induced sputum, and bronchoalveolar lavage fluid from patients at risk for or with acquired immunodeficiency syndrome.

The recovery rates of cytomegalovirus from mucolysed induced sputum samples and bronchoalveolar lavage fluid obtained from individuals at risk for or with acquired immunodeficiency syndrome were compared. It was demonstrated that cytomegalovirus could be reliably recovered from mucolysed induced sputum, and such recovery was highly predictive of recovery from bronchoalveolar lavage samples obtained from the same individual.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Unexpected isolation of Bordetella pertussis from patients with acquired immunodeficiency syndrome.

We isolated Bordetella pertussis from three patients with acquired immunodeficiency syndrome who underwent diagnostic bronchoscopy for evaluation of respiratory symptoms. The B. pertussis isolates were recovered from medium (charcoal-yeast extract agar) formulated to enhance recovery of Legionella spp., and one of the isolates stained positively with antisera directed against Legionella spp.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Stool diagnosis of giardiasis using a commercially available enzyme immunoassay to detect Giardia-specific antigen 65 (GSA 65).

A commercially available enzyme immunoassay for the diagnosis of giardiasis was evaluated in a clinical trial. The ProSpecT/Giardia diagnostic test (Alexon, Inc., Mountain View, Calif.) was compared with the standard ova and parasite (O&P) microscopic examination. Additionally, several widely used stool fixatives and a commonly used transport medium were assessed for compatibility with the immunoassay. A total of 325 stool specimens were collected and used to evaluate assay performance. Of those, 93 specimens were collected from symptomatic Giardia O&P-positive patients and 232 specimens were randomly collected from patients as part of a routine health screening procedure. All 93 Giardia O&P-positive stool specimens were strongly positive by visual and spectrophotometric examination using the immunoassay. Of the 232 randomly collected specimens, 16 were positive by O&P examination and immunoassay, 6 were negative by O&P examination but positive by immunoassay, and 1 was positive by O&P examination and negative by immunoassay. There was substantial supportive evidence that indicated that the six immunoassay-positive, O&P-negative specimens were true-positives. When these six specimens were accepted as true-positives, the immunoassay detected almost 30% more cases of Giardia infection than did O&P examination. Its sensitivity and specificity were 96 and 100%, respectively, while the sensitivity and specificity of O&P examination were 74 and 100%, respectively. The immunoassay also performed well on specimens treated with 10% neutral Formalin, sodium acetate-Formalin fixative, and Cary-Blair transport medium. However, the test was not compatible with polyvinyl alcohol-treated specimens. Overall, the ProSpecT/Giardia test was a sensitive, specific immunoassay which was easy to run and interpret. It offers a simple solution to traditional difficulties encountered in diagnosing Giardia infection.

Animals↗
PubMed1989

Killing by antimycobacterial agents of AIDS-derived strains of Mycobacterium avium complex inside cells of the mouse macrophage cell line J774.

The murine macrophage continuous cell line J774 was used to measure the ability of antimicrobial agents, either singly or in combination, to kill intracellular Mycobacterium avium complex. All of 14 strains of M. avium complex, isolated from patients with AIDS, grew inside J774 cells during an incubation period of 7 days. The susceptibility of macrophage-ingested M. avium complex to antimicrobial agents was determined by comparing the number of colony-forming units (cfu) of M. avium complex inside untreated macrophages at the time of drug addition with the number of cfu present in macrophages after treatment with drugs for 7 days. Simultaneous experiments were carried out in broth medium without macrophages in order to compare killing of free mycobacteria with killing of macrophage-ingested mycobacteria. Antimicrobial agents (rifampin, rifabutin [Ansamycin], ethambutol, ciprofloxacin, clofazimine, isoniazid, and amikacin) were tested using concentrations that are achievable in the serum of patients. Among drugs known to penetrate macrophages, there was 96.2% agreement in susceptibility test results between the broth experiments and the J774 experiments when single drugs were tested, but only 74% agreement when combinations of drugs were tested. Killing of M. avium complex inside J774 cells by any single drug was uncommon. However, killing in J774 cells occurred against 10 of 11 (91%) strains with the combination of rifabutin + ethambutol + ciprofloxacin and against all of seven strains tested with the combination of rifabutin + ethambutol + amikacin. Interpretive criteria of in vitro susceptibility data need to be developed so that these interpretations correlate with a predictable clinical response in patients.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Organization of microbiology laboratory services for the diagnosis of pulmonary infections in patients with human immunodeficiency virus infection.

When faced with the ever-increasing demand for the rapid laboratory diagnosis of Pneumocystis carinii pneumonia (PCP), as well as a variety of fungal, parasitic, and bacterial opportunistic infections in Human Immunodeficiency Virus (HIV)-infected individuals, the Chest Service and the Clinical Microbiology Laboratory at San Francisco General Hospital developed a coordinated plan for the collection and rapid examination of specimens to allow presumptive diagnoses to be made as quickly as possible. Clinical studies have been performed to determine the efficacy of different specimens and diagnostic systems for the provision of clinically useful information. Our approach has been to provide medical care on an outpatient basis using less invasive diagnostic systems that do not require direct physician participation. Direct laboratory examination of a single specimen submitted to microbiology often yielded presumptive or final diagnoses that were directly communicated to the physician. The evolution of PCP diagnosis in AIDS patients is described. Our current procedure of examining mucolysed, concentrated induced sputum stained with a rapid Giemsatype stain, Diff-Quik (Baxter/Scientific Products, McGaw, IL), has a sensitivity for P carinii detection of 74% to 77%. We have found that the use of commercially available immunofluorescence staining diminishes screening time and increases the sensitivity of P carinii detection in mucolysed concentrated induced sputum. We also describe the appearance of bacterial, fungal, and parasitic agents seen on direct examination and the usefulness of antigen detection, serology, and various microbiologic culture systems for diagnosing infections caused by these organisms.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Infection of the health-care worker by HIV and other blood-borne viruses: risks, protection, and education.

Transmission of the human immunodeficiency virus (HIV) and other blood-borne viruses in hospitals is discussed, and the infection control system and worker protection and education plan at San Francisco General Hospital (SFGH) are described. The acquired immunodeficiency syndrome (AIDS) epidemic has led to increased concern about occupationally acquired infections in health-care workers. As the number of HIV-infected persons increases, so does the risk of infection. Occupationally acquired HIV infection of health-care workers occurs principally in nurses, phlebotomists, and laboratory technicians through accidental subcutaneous injection of contaminated blood; splashing of blood onto open skin lesions, the eyes, and mucous membranes represents another route of exposure. The risk of infection from a single needle-stick exposure to HIV-infected blood is about 0.4%. Other blood-borne viruses to which employees are vulnerable include hepatitis B virus and human T-cell lymphotropic viruses, which may cause leukemia and lymphoma. SFGH has a comprehensive infection control system. Specimen containers are enclosed in transparent secondary containers, the worker is encouraged to wear protective clothing when necessary, and specific needle-stick precautions are promoted. There is also a health-care worker protection and education plan. The employee health services department provides immunizations, keeps records on accidental exposures, and operates a hot line. The education committee disseminates educational materials and arranges lectures. Infection control and education provide simple but effective measures for protecting hospital employees against HIV and other occupationally acquired infections.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The use of mucolysed induced sputum for the identification of pulmonary pathogens associated with human immunodeficiency virus infection.

We describe a system for diagnosis of pulmonary disease in the human immunodeficiency virus-infected patient using induced sputum and other diagnostic procedures. This system has been successfully used at San Francisco (Calif) General Hospital for more than 2 years. It utilizes outpatient facilities and reduces the need for bronchoscopy. Sputum induced by inhalation of 3% saline mist, mucolysed, concentrated by centrifugation, and stained by a rapid modified Giemsa stain was the first diagnostic specimen examined in 404 episodes of suspected human immunodeficiency virus-associated pulmonary disease in 358 patients. Pneumocystis carinii was found in 222 (55%) sputum specimens. In 118 episodes in which the sputum did not contain P carinii, bronchoscopy with transbronchial biopsy and/or bronchoalveolar lavage was performed and P carinii was found in 50 (42%). These 118 bronchoscopy results, as well as evaluation of the subsequent clinical course of those patients who accounted for 64 episodes of lung disease and who did not have bronchoscopy following examination of nondiagnostic induced sputum, indicated a range of sensitivity for detection of P carinii in induced sputum of 74% to 77% and a negative predictive value of 58% to 64%. Mycobacteria were recovered from 11 (6%) of the induced sputum and 6 (12%) of the bronchoscopic specimens containing P carinii. However, only oral or environmental fungi were recovered from P carinii-containing induced sputum or bronchoscopic specimens. For those patients in whom P carinii was not detected, only the bronchoscopic specimens were cultured for Mycobacteria and fungi. Potentially pathogenic Mycobacteria and fungi were recovered from 16 (23.5%) and 34 (50%), respectively, of these P carinii-negative specimens. Analysis of these results, obtained under routine practice conditions, indicates that bronchoscopy should be reserved for those patients whose induced sputum examinations do not show P carinii and that mycobacterial and fungal cultures be performed only on bronchoscopic specimens in which P carinii is not detected.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Diagnosis of Pneumocystis carinii pneumonia: improved detection in sputum with use of monoclonal antibodies.

With the dramatic increase in the frequency of Pneumocystis carinii pneumonia associated with human immunodeficiency virus infection, there has been a need for more rapid and less invasive diagnostic techniques. Recent studies have shown that examination of induced sputum can establish the diagnosis of P. carinii pneumonia in about 55 percent of cases. To assess whether a recently developed indirect immunofluorescent stain using monoclonal antibodies was more sensitive than Giemsa or toluidine blue O stains in detecting P. carinii in sputum, we undertook two prospective studies. Of 63 patients at one institution from whom sputum specimens were obtained, 49 were ultimately given a diagnosis of P. carinii pneumonia, 46 of them by staining of sputum. The sensitivity of the three stains in detecting P. carinii was 45 of 49 (92 percent) for immunofluorescence; 37 of 49 (76 percent) for Diff-Quik (a Giemsa-type stain); and 39 of 49 (80 percent) for toluidine blue O. There were no false positive immunofluorescent stains. In a similar study of a series of 25 patients at another institution, a diagnosis of P. carinii pneumonia was made in 23 of 25 patients by staining of induced sputum. We conclude that examination of induced sputum is a rapid, sensitive, and inexpensive method for diagnosing P. carinii pneumonia and that indirect immunofluorescence is a practical and highly sensitive staining technique for establishing this diagnosis.

Animals↗
PubMed1988

Rectal leishmaniasis in a patient with acquired immunodeficiency syndrome.

A severe rectal lesion due to Leishmania infection is described in an American-born homosexual man with the acquired immunodeficiency syndrome. The infection, which may have been venereally transmitted, responded to treatment with amphotericin B. There was no evidence of visceral leishmaniasis. The contribution of the patient's immunodeficiency to the development of the atypical cutaneous leishmanial lesion is unclear. The case may foretell increasing problems with protozoan infections in AIDS as the epidemic spreads to areas with endemic protozoan diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Antimicrobial synergism against Mycobacterium avium complex strains isolated from patients with acquired immune deficiency syndrome.

Pairs of 11 antimicrobial agents were tested in vitro for their ability to act synergistically against three strains of Mycobacterium avium complex isolated from patients with acquired immune deficiency syndrome. From the combinations tested, four drugs (ethambutol, rifampin, ciprofloxacin, and erythromycin) were selected for more extensive study against 20 strains of M. avium complex. The inhibitory and killing synergism obtained with combinations of two, three, or four drugs was assessed by determining the fractional inhibitory concentration index and fractional bactericidal concentration index. Inhibitory synergism occurred against 90 to 100% of the strains for all drug combinations in which ethambutol was included. Killing synergism occurred against 85 to 95% of the strains when ethambutol was used in combinations which included either rifampin or ciprofloxacin. However, killing synergism occurred against only 45% of the strains when drugs were tested at concentrations that can be obtained in patient serum. In other experiments, rifabutin (Ansamycin) gave results that were comparable to those obtained with rifampin. Clofazimine did not show synergistic killing activity at a concentration that is achievable in serum for any of the drugs tested. Our results indicate that there is considerable variability in the antimicrobial susceptibility of M. avium isolates obtained from patients with acquired immune deficiency syndrome. This variability could have significant impact on the clinical response to various therapies.

Acquired Immunodeficiency Syndrome↗
PubMed1988

High titer anti-HIV antibody reactivity associated with a paraprotein spike in a homosexual male with AIDS related complex.

We observed a human immunodeficiency virus (HIV)-infected homosexual male with AIDS related complex (ARC) who had a serum globulin level of 80 g/L. Serum protein electrophoresis revealed a gamma globulin fraction of 40 g/L, of which 50% (20 g/L) was contained within a paraprotein spike, comprised predominantly of IgG kappa. This patient also had high titer anti-HIV antibodies in his serum, which were Western blot reactive at a final dilution of 1:500,000, and recognized gp120env, p66pol, p55gag, p53pol, p41gag, and p24gag. Because paraproteins in the past have been shown to be directed against specific antigens, we purified this patient's paraprotein using a modified high performance liquid chromatography (HPLC)-hydroxylapatite procedure and tested the purified paraprotein for anti-HIV antibody activity. The purified paraprotein retained anti-HIV antibody activity to a final dilution of 1:100,000, and recognized p66pol, p55gag, p53pol, p41gag, and p24gag. The recognition of both "gag" and "pol" gene products suggested that the purified paraprotein might not be monoclonal in origin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that the purified paraprotein contained at least two immunoglobulin light chain species (Mol wt 30 to 33 Kd). Affinity chromatography of the purified paraprotein using a p24-Sepharose 4B matrix separated the "gag" and "pol" antibody activities. Immunoglobulin gene rearrangement analysis of a bone marrow aspirate (which contained 15% plasma cells) failed to reveal a clonal population of immunoglobulin producing cells. We conclude that this patient's paraprotein accounted for most of the anti-HIV activity present in whole serum, and that this paraprotein was not monoclonal in origin.

AIDS-Related Complex↗