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Biomedical subjects

J L Johnson

Publications and source records attributed to J L Johnson.

At least 109 records · Page 6Linked to original sources

Gas chromatography/mass spectrometry identification and quantification of isazophos in a famphur pour-on and in bovine tissues after a toxic exposure.

A sample identified as "Warbex pour-on," expected to contain 13.2% famphur, and bovine tissue samples from 2 heifers that died after exhibiting signs of organophosphate intoxication were analyzed by gas chromatography/mass spectrometry (GC/MS). A product formulation problem was suspected because brain cholinesterase activities were depressed in both animals. Electron impact (EI) GC/MS of the pour-on revealed 9.7% famphur and an unidentified peak with approximately 76% of the peak area of the famphur. The unidentified peak showed a molecular ion at m/z 313, with a single Cl isotope cluster. Methane chemical ionization (MeCI) MS confirmed the molecular weight at 313 (1 Cl). A search on the molecular formula C9H17N3O3PSCl yielded a single match, isazophos. EI and MeCI GC/MS of reference isazophos confirmed the identity of the suspect peak. The concentration of isazophos in the pour-on was determined to be 6.0%. Famphur and isazophos were identified by their EI spectra and GC retention times in extracts of liver and brain from the 2 deceased animals. A GC/MS procedure utilizing selected ion monitoring (SIM) was developed for quantification of isazophos in liver, kidney, muscle, and fat of additional affected animals sacrificed at various times after exposure. Isazophos remained in animal tissues for as long as 94 days after topical exposure. Isazophos was present in fetal liver 70 days after exposure of the dam. High levels (6-3,500 ppm) of isazophos and famphur remained on the skin at 39 days postexposure.

Animals↗

Serial causation: occasion setting in a causal induction task.

The temporal relations among candidate causes were studied in a causal induction task using a design that is known to produce occasion setting in animal learning preparations. For some subset of the observations, one event, the occasion setter, was accompanied by another event, the conditional cause; for another subset of the observations, the conditional cause occurred alone. The efficacy of the conditional cause depended on whether it was or was not accompanied by the occasion setter. Participants used the occasion setter to modulate their effect expectancy to the conditional cause when the events were presented serially, but not simultaneously. Current causal induction models are unable to account for the full range of effects that we observed; the relative roles of time, attention, and cue distinctiveness are discussed.

Association Learning↗

Viral pneumonias. Multifaceted approach to an elusive diagnosis.

Despite enhanced laboratory techniques such as viral culture, rapid antigen detection, and gene amplification, a confident diagnosis of viral pneumonia continues to be a challenge. The nonspecific nature of clinical characteristics and the extreme sensitivity of laboratory techniques make the diagnosis difficult, even when a viral agent is detected. Understanding the limitations of these technological advances and the use of histopathologic techniques can greatly enhance a skilled clinician's ability to make an accurate diagnosis.

Antigens, Viral↗

Viral pneumonias. Infection in the immunocompromised host.

Three herpesviruses--herpes simplex, varicella-zoster, and cytomegalovirus--commonly cause respiratory tract infections in immunocompromised patients. Adenoviruses and measles virus are also significant causes of respiratory disease in this population. Diagnosis of herpesvirus infections is difficult because these viruses can establish latency and are often shed intermittently in the absence of invasive disease. A positive respiratory tract culture of herpesviruses alone is not diagnostic of active invasive disease. Preventive measures should focus on limiting the patient's exposure to active infection, broad use of available vaccines in children and susceptible adults, and use of hyperimmune globulin and chemoprophylaxis in high-risk patients. Adenovirus pneumonia is diagnosed by viral culture and rapid antigen detection assays, whereas measles pneumonia is often identifiable by the characteristic rash. Treatment of either adenovirus or measles pneumonia is primarily supportive.

Adult↗

Viral pneumonias. Epidemic respiratory viruses.

Influenza, respiratory syncytial, and parainfluenza viruses usually cause mild, self-limited illness in adults. However, elderly and immunocompromised persons are at increased risk for development of severe pneumonia. Clinical and radiographic features of epidemic viral pneumonias are often nonspecific. Newer and faster methods of viral culture and viral antigen detection have improved the capability for definitive diagnosis in recent years. Preventive measures for influenza virus pneumonia center on limiting exposure of high-risk patients to active cases of influenza, administering annual vaccinations, and providing chemoprophylaxis. Prophylaxis against RSV is effective in preventing complications. No effective vaccines have been developed against RSV or parainfluenza. Therapy for viral pneumonia is primarily supportive. Amantadine may be beneficial for influenza virus pneumonia, and ribavirin may be useful for RSV and parainfluenza virus disease. However, further definitive studies are necessary to determine their roles in these viral pneumonias.

Adult↗

Pleural effusions in cardiovascular disease. Pearls for correlating the evidence with the cause.

In patients with cardiomegaly and signs and symptoms compatible with CHF, unilateral right-sided or bilateral pleural effusions of similar size are likely to be due to left-sided CHF. Isolated right ventricular failure or chronic pulmonary hypertension is not usually associated with pleural effusions, and unrecognized or new-onset left ventricular dysfunction and other causes should be considered when a patient with cor pulmonale presents with a pleural effusion. Unilateral left-sided pleural effusions with cardiomegaly may be due to pericardial disease. Current hypotheses do not adequately explain the laterality of effusions in CHF or pericardial disease. Clinical and radiographic correlation is always required; however, the associations described occur often enough to make them useful in day-to-day clinical practice. When ascribing pleural effusions to CHF, clinicians must be sure the clinical signs and history "fit the picture," because pneumonia and pulmonary embolism may also cause pleural effusions in patients with heart failure. Typical pleural effusions in patients with uncomplicated CHF (demonstrated by small to medium-sized effusions and the absence of fever, leukocytosis, pleuritic chest pain, or marked asymmetry in bilateral effusions) do not require routine diagnostic thoracentesis for evaluation. A reasonable approach in such cases is treatment of the underlying CHF and follow-up radiography to monitor for resolution of the effusions. Prompt diagnostic thoracentesis is indicated whenever atypical features are present and other diagnoses are under consideration.

Cardiovascular Diseases↗

Slowly resolving and nonresolving pneumonia. Questions to ask when response is delayed.

What is the proper course of action when pneumonia symptoms seem to linger? Is the disease running a typical course, or is further evaluation needed? Dr Johnson addresses these important questions with an outline of risk factors for delayed resolution and a detailed listing of diagnostic considerations. He also discusses reasonable timing of further studies and the usefulness of radiography and fiberoptic bronchoscopy.

Adult↗

Determination of drug susceptibility and DNA fingerprint patterns of clinical isolates of Mycobacterium tuberculosis from Kampala, Uganda.

OBJECTIVE: To ascertain the rate of initial drug resistance and transmission patterns of Mycobacterium tuberculosis in Kampala, Uganda. SETTING: National Tuberculosis (TB) Treatment Centre, Mulago Hospital, Kampala, Uganda and Case Western Reserve University, Cleveland, Ohio, USA and McClellan Memorial Veterans Hospital, Little Rock, Arkansas, USA. METHODS: Using a radiometric BACTEC 460 TB system, susceptibility of 215 M. tuberculosis isolates from previously untreated patients from Kampala, Uganda (age range, 17-48 years, mean, 28 years; 56% males and 69% human immunodeficiency virus (HIV)-seropositive) was determined for isoniazid, rifampin, streptomycin and ethambutol. Isolates from 73 patients, selected on the basis of geographical location, were tested for strain diversity or relatedness using the IS6110 DNA fingerprinting technique. RESULTS: Resistance rates were as follows: isoniazid, 7.9% streptomycin, 6.1% rifampin, 1.4% and ethambutol 0.9%. Twelve per cent of the strains were resistant to at least one of the first line drugs tested and 4.7% were multiply resistant. There were no significant differences in resistance rates between patients with and without HIV infection. Using the number and size of DNA fragments containing IS6110, only three clusters of isolates with identical RFLP patterns were found out of the 73 isolates tested (8.2%). Each cluster contained two isolates. Three (4.1%) isolates had less than seven copies of IS6110. CONCLUSION: This study shows that in Uganda initial drug resistance rates to anti-tuberculosis agents are low and similar to other sub-Saharan African countries and that multiple strains of M. tuberculosis have been transmitted within the community.

AIDS-Related Opportunistic Infections↗

Quantitative sputum bacillary load during rifampin-containing short course chemotherapy in human immunodeficiency virus-infected and non-infected adults with pulmonary tuberculosis.

SETTING: National Tuberculosis (TB) Treatment Centre, Mulago Hospital and Joint Clinical Research Centre, Kampala, Uganda. OBJECTIVE: To compare the quantitative sputum bacillary load between TB patients infected with the human immunodeficiency virus (HIV) and those non-infected, during treatment with standard short course chemotherapy (SCC). DESIGN: To compare clinical characteristics and quantitative sputum bacillary load as measured by quantitative acid-fast bacilli (AFB) smears, colony forming unit (cfu) assay and time until positive culture in the BACTEC radiometric liquid system between 14 HIV-infected and 22 non-HIV-infected adults with initial episodes of smear-positive pulmonary TB at baseline and during treatment with standard four-drug SCC. RESULTS: Other than cavitation (P = 0.042) and adenopathy (P = 0.03), which were more common among non-HIV-infected and HIV-infected patients, respectively, there were no significant differences in baseline demographic, clinical, radiological and laboratory characteristics between the groups. Mean pretreatment sputum bacillary burden (6.5+/-0.51 log10 AFB/ml, 5.91+/-0.91 log10 cfu/ml and 1.8+/-1.7 days until positive BACTEC culture for HIV-infected patients and 6.32+/-0.85 log10 AFB/ml, 5.58+/-0.68 log10 cfu/ml and 1+/-1.2 days until positive BACTC culture for non-HIV-infected patients) were comparable between HIV-infected and non-HIV-infected patients. Clinical and bacteriological responses to standard SCC and treatment outcome did not differ between the groups. CONCLUSION: Quantitative sputum bacillary load at baseline and during SCC did not differ significantly between HIV-infected and non-HIV-infected adults with initial episodes of smear-positive TB.

AIDS-Related Opportunistic Infections↗

Subungual melanoma. A review of 93 cases with identification of prognostic variables.

From 1970 to 1996, 93 patients received diagnoses of subungual melanoma. Followup data were complete on all patients and reviewed with a median duration of followup of 5.2 years. This study identifies significant clinicopathologic variables that affect survival and provides the orthopaedic surgeon assistance in the early diagnosis and treatment of this lesion. Eight-three percent of patients presented with Stage I disease, whereas 17% had nodal or distant disease. Fifty-three percent had locally advanced disease at presentation. Twelve percent of the patients were African-American. Fifty-five percent of the lesions arose on the hands with thumb involvement predominating in more than half of these cases. Operative therapy consisted of amputation. Elective lymph node dissection was performed in 34 patients (37%) for Stage I tumors of intermediate thickness. Therapeutic node dissection was required in 16 patients (17%) for positive nodes. Five-year survival was 74% for patients with Stage I disease and 40% for patients with Stage II disease. Statistical analysis identified stage at diagnosis, Clark and Wihm's level, the patient's race, and the presence of ulceration as prognostic variables affecting survival. The diagnosis of subungual melanoma carries a grave prognosis and often is misdiagnosed in the early stages. The treatment of choice is amputation at the appropriate level.

Adolescent↗

Efficacy of an unsupervised 8-month rifampicin-containing regimen for the treatment of pulmonary tuberculosis in HIV-infected adults. Uganda-Case Western Reserve University Research Collaboration.

SETTING: National Tuberculosis Treatment Centre, Mulago Hospital, Kampala, Uganda. OBJECTIVE: To assess the efficacy of a daily, self-administered 8-month rifampicin-containing regimen for the treatment of pulmonary tuberculosis (TB) in human immunodeficiency virus (HIV) infected adults. DESIGN: Treatment outcomes in patients with pulmonary TB treated with a single 8-month regimen and followed in a prospective epidemiological study. RESULTS: Two hundred and sixty-five HIV-infected and 26 non-HIV-infected adults with initial episodes of pulmonary tuberculosis were treated with 2 months of daily isoniazid (INH), rifampicin (RMP), ethambutol and pyrazinamide followed by 6 months of daily INH + RMP. Median follow-up was 17.8 months. Ninety-five per cent of the HIV-infected and all of the non-HIV-infected patients who had sputum examined were sputum culture negative after 2 months of treatment. Twenty-two HIV-infected and no non-HIV-infected patients died during treatment. Relapse rates were 8.4% (5.9 per 100 person-years of observation [PYO], 95%CI 3.2-8.6) among HIV-infected patients and 4.5% (2.1/100 PYO, 95%CI 0-7.8) for non-HIV-infected patients. Adverse drug reactions occurred in 37% of the HIV-infected patients; most were minor and self-limiting. CONCLUSION: An 8-month RMP-containing regimen was well tolerated and effective in the treatment of HIV-infected adults with initial episodes of pulmonary TB. Relapse rates were similar to those reported with 6-month short-course regimens in HIV-infected individuals. Decisions about the duration of anti-tuberculosis treatment for HIV-infected adults must balance programme resources and the likelihood of poor compliance with longer regimens with the potential for a modest decrease in relapses with longer treatment.

AIDS-Related Opportunistic Infections↗

Simultaneous comparison of reactivity to purified protein derivative RT-23 and Tubersol in health care workers in Vitória, Brazil.

Questions have recently been raised regarding the potency of purified protein derivative (PPD) RT-23, the tuberculin most widely used world-wide for skin testing. We performed simultaneous testing with PPD RT-23 and Tubersol to compare these reagents during a tuberculin survey of 202 adult health care workers at a large teaching hospital in 1997. Individuals were tested with 2 tuberculin units (TU) PPD RT-23 and 5 TU Tubersol using the Mantoux method. Using a 10 mm cut-point for a positive PPD test, 39% of the health care workers were positive when tested with Tubersol and 35% were positive when tested with PPD RT-23. The median PPD size with Tubersol was 4 mm (interquartile range = 0-12 mm) compared to 2 mm (interquartile range = 0-12 mm) with PPD RT-23. PPD skin test reactivity with the two reagents was highly correlated (Spearman's rank coefficient, rho = 0.92; P = 0.01, two tailed). Concordance between the skin test reaction size with the two antigens did not differ based on age, sex or prior BCG vaccination. Mantoux skin test reactivity in health care workers in an area with a high prevalence of tuberculosis was comparable with PPD RT-23 and Tubersol.

Adolescent↗

An unusual case of corneal perforation secondary to Pseudomonas keratitis complicating a patient's surgical/trauma intensive care unit stay.

We report a case of corneal perforation secondary to bacterial keratitis caused by Pseudomonas aeruginosa in a trauma patient in our intensive care unit. A 43-year-old man was involved in a motorcycle crash and suffered multiple injuries necessitating a prolonged intensive care unit (ICU) stay. Subsequently P. aeruginosa was cultured from his sputum, blood, and open abdomen. He developed a bacterial keratitis in his right eye, which also grew P. aeruginosa. This infection rapidly progressed to corneal perforation requiring a Gunderson conjunctival flap and lateral tarsorrhaphy in addition to aggressive antibiotic treatment. At the time of discharge from the hospital the patient had the return of vision to light only in his right eye. Corneal perforation is an unusual event in the ICU. Prevention or early detection of bacterial keratitis with aggressive antibiotic treatment is needed to prevent such complications. Pseudomonas is one of the more virulent organisms that can infect the cornea and early identification is paramount for a good outcome. Management of this complicated case is discussed and the limited amount of literature on nosocomial bacterial keratitis in the ICU is reviewed.

Adult↗

How does positive end-expiratory pressure decrease pulmonary CO2 elimination in anesthetized patients?

In anesthetized, mechanically ventilated patients, 10 cm H2O positive end-expiratory pressure (PEEP10) immediately decreased the CO2 volume exhaled per breath (V(CO2,br)) by 96%, as exhaled tidal volume (VT) decreased to expand functional residual capacity during the first 8 breaths after PEEP10 began. Then, the sustained decrease in V(CO2,br) for over 10 min was due to the 19% decrease in cardiac output (QT, decreased CO2 delivery from tissues to lung) and to the decrease in alveolar ventilation (VA). In turn, decreased VA resulted from decreased VT (loss of inspired volume into the compressible volume of the ventilating circuit) and possibly from increased physiological dead space, due to the potential for new high alveolar ventilation-to-perfusion (VA/Q) lung regions. V(CO2,br) increased and recovered to baseline by 20 min of PEEP10 ventilation because QT increased to augment the CO2 delivery to the lung and alveolar P(CO2) increased (increased mixed venous P(CO2) and tissue CO2 retention) to increase V(CO2,br) while alveolar VT remained depressed. End-tidal P(CO2) (PET(CO2) progressively increased during PEEP10 and did not detect the decrease in V(CO2,br) during PEEP10 ventilation because PET(CO2) does not account for exhaled volume.

Anesthesia↗

Enhanced efficiency of ATP hydrolysis during nitrogenase catalysis utilizing reductants that form the all-ferrous redox state of the Fe protein.

The amount of MgATP hydrolyzed per pair of electrons transferred (ATP/2e) during nitrogenase catalysis (1.0 atm N(2), 30 degrees C) using titanium(III) citrate (Ti(III)) as reductant was measured and compared to the same reaction using dithionite (DT). ATP/2e values near 2.0 for Ti(III) and 5.0 for DT indicate that nitrogenase has a much lower ATP requirement using Ti(III) as reductant. Using reduced Azotobacter vinelandii flavoprotein (AvFlpH(2)), a possible in vivo nitrogenase reductant, ATP/2e values near 2.0 were also observed. When the reaction was conducted using Ti(III) under N(2), 5% CO in N(2), Ar, 5% CO in Ar, or acetylene, ATP/2e values near 2.0 were also observed. With Ti(III) as reductant, ATP/2e values near 2.0 were measured as a function of temperature, Fe:MoFe protein ratio, and MoFe:Fe protein ratio, in contrast to measured values of 4.0-25 when DT is used under the same conditions. Both Ti(III) and AvFlpH(2) are capable of forming the [Fe(4)S(4)](0) cluster state of the Fe protein whereas DT is not, suggesting that ATP/2e values near 2.0 arise from operation of the [Fe(4)S(4)](2+)/[Fe(4)S(4)](0) redox couple with hydrolysis of only 2 ATPs per pair of electrons transferred. Additional experiments showed that ATP/2e values near 2. 0 correlated with slower rates of product formation and that faster rates of product formation produced ATP/2e values near 5.0. ATP/2e values of 5.0 are consistent with the operation of the [Fe(4)S(4)](2+)/[Fe(4)S(4)](1+) redox couple while ATP/2e values of 2.0 could arise from operation of the [Fe(4)S(4)](2+)/[Fe(4)S(4)](0) redox couple. These results suggest that two distinct Fe protein redox couples may be functional during nitrogenase catalysis and that the efficiency of ATP utilization depends on which of these redox couples is dominant.

Adenosine Triphosphate↗

Sequential chemotherapy (etoposide, vinblastine, and doxorubicin) and subtotal lymph node radiation for patients with localized Hodgkin disease and unfavorable prognostic features: A phase II Cancer and Leukemia Group B Study (9051).

BACKGROUND: The aim of this study was to evaluate a regimen of sequential chemotherapy and radiotherapy for patients with Hodgkin disease. METHODS: The Cancer and Leukemia Group B conducted a Phase II study of three cycles of etoposide, vinblastine, and doxorubicin (EVA) chemotherapy followed by subtotal lymph node radiation for patients with localized Hodgkin disease and unfavorable prognostic features. Fifty-nine patients were enrolled in the study. Fifty-three patients met all study eligibility criteria; 48 of them (91%) had mediastinal disease and 29 (55%) had bulky mediastinal disease. RESULTS: A complete response (CR) occurred in 35 of the patients (66%). Of all patients who had CR, 26% had the CR after the chemotherapy and before the radiation, and 74% after the chemotherapy and radiation. Twenty percent of the patients who had CR experienced disease progression; in these patients, the progression was outside the radiotherapy field in the lung and involved widespread disease. CONCLUSIONS: EVA offers a nonbleomycin-containing alternative for patients in whom preexisting pulmonary disease may be exacerbated by bleomycin and radiation therapy. EVA, as given in this study (in three cycles), was insufficient chemotherapy for patients who had disease in areas outside the radiation fields (occult disease).

Adolescent↗