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Biomedical subjects

D H Walker

Publications and source records attributed to D H Walker.

At least 217 records · Page 12Linked to original sources

Pathologic and virologic study of fatal Lassa fever in man.

Postmortem examination of 21 virologically documented cases of Lassa fever, including 6 complete autopsies, was performed as part of a field study of community-acquired Lassa fever in Sierra Leone. The most consistently observed lesions were hepatocellular, adrenal, and splenic necrosis and adrenal cytoplasmic inclusions. Neither these lesions, nor other milder and less constantly observed lesions such as myocarditis, renal tubular injury, and interstitial pneumonia, appeared severe enough to explain the cause of death in Lassa fever. The central nervous system (CNS) contained no specific lesions. Viral titrations demonstrated high viral content in liver, lung, spleen, kidney, heart, placenta, and mammary gland. Clinical laboratory data included elevation of hepatic enzymes, creatine phosphokinase (CPK), and blood urea nitrogen (BUN). Because of the paucity of pathologic lesions in spite of widely disseminated viral infection, further investigation of humoral inflammatory mechanisms is indicated.

Adult↗

The occurrence of eschars in Rocky Mountain spotted fever.

Two patients with fatal, laboratory-confirmed Rocky Mountain spotted fever (RMSF) were noted early in their course to have a skin lesion characteristic of a rickettsial eschar. Postmortem immunofluorescent and histopathologic studies demonstrated that the lesions were sites of extensive contiguous infection by Rickettsia rickettsii with associated injury to numerous local blood vessels. Rickettsial vasculitis and occlusive luminal thrombosis were associated with dermal and epidermal coagulative necrosis forming the eschars. Both eschars were noted to be the sites of a bite. In one case the arthropod was identified as a tick. The clinical importance of the search for an eschar in a patient suspected of having RMSF is that diagnostic skin biopsy immunofluorescent demonstration of R. rickettsii may be performed prior to the onset of the rash.

Adolescent↗

The liver in Rocky Mountain spotted fever.

Hepatic tissues from nine patients who had fatal Rocky Mountain spotted fever were examined in sequential sections by brightfield and immunofluorescence microscopy for histologic lesions and for coincidence of these lesions with the distribution of Rickettsia rickettsii. The basic hepatic lesion in Rocky Mountain spotted fever is an inflammation of the portal triad in which large mononuclear cells and neutrophils predominate. Rickettsia were demonstrated in lesions of the portal triads in eight of nine cases. Inflammation of the portal triad and sinusoidal erythrophagocytosis showed a strong relationship to the presence of the disease state when comparisons with age- and sex-matched control subjects were made. Hepatocellular necrosis was not found to be an important pathologic feature of the disease. Elevated serum bilirubin values and jaundice are likely to be due to a combination of duct obstruction secondary to inflammation and edema of portal triads, and hemolysis.

Adolescent↗

Fusarium infection in burned patients.

The incidence of fungal infections of burn wounds is increasing because of the dramatic improvement in antibacterial chemotherapy and burn wound care. Species of Fusarium, common soil fungi and plant pathogens, are rarely isolated from burn wounds, and invasive disease due to these organisms is also rare. Therefore, a case of burn wound infection with dissemination due to F. oxysporum is reported; three other cases of burn wound colonization by Fusarium sp. are also reported. The literature on fungal infections of burn wounds is reviewed, and the importance of combined histologic and mycologic studies in the evaluation of such wounds is discussed.

Adolescent↗

American mucocutaneous leishmaniasis. Culture of a Leishmania species from peripheral blood leukocytes.

A Leishmania species was recovered in culture from the buffy coat of peripheral blood of a patient who had American mucocutaneous leishmaniasis, although cultures of biopsy material from the skin lesions were unsuccessful. Blood culture has not previously been recommended in non-visceral leishmaniasis. The importance of recognizing this tropical disease is stressed. Blood culture may be useful in confirming the diagnosis.

Culture Techniques↗

Pseudodiphtheria: prominent pharyngeal membrane associated with fatal paraquat ingestion.

Three patients presented with prominent pharyngeal membranes suggestive of tonsillar-pharyngeal diphtheria, but later found to be caused by oral ingestion of the herbicide paraquat. In all cases appropriate therapy was delayed because of failure to include paraquat in the differential diagnosis: Paraquat ingestion should be considered in all patients with prominent tongue and pharyngeal membranes.

Adult↗

Rickettsial infection of the pulmonary microcirculation: the basis for interstitial pneumonitis in Rocky Mountain spotted fever.

Pulmonary tissue from 10 patients with fatal Rocky Mountain spotted fever was examined by brightfield microscopy for histopathologic lesions and by immunofluorescence for Rickettsia rickettsii. The distribution of rickettsiae and the vasculitis of the pulmonary microcirculation coincided. The lungs demonstrated the consequent interstitial pneumonia--alveolar septal congestion and interstitial edema; alveolar edema, fibrin, macrophages, and hemorrhage; and interlobular septal edema. The effects of the rickettsial damage to the pulmonary microcirculation are an important component of the pathophysiology of severe Rocky Mountain spotted fever. The distribution of rickettsial organisms within the lung indicates that person to person aerosol transmission is extremely unlikely.

Adolescent↗

Laboratory diagnosis of Rocky Mountain spotted fever.

To examine the use of the laboratory in the diagnosis of Rocky Mountain spotted fever and to determine the specificity and sensitivity of the Weil-Felix test, hemagglutination, complement fixation, and skin biopsy immunofluorescence in the hospital, we reviewed our experience during th year 1978. Sera were submitted from 142 patients and skin biopsies from 16 patients suspected of having RMSF. Sensitivity rates of methods in the acute phase were skin biopsy, 70%; Proteus OX-19 agglutination, 65%; hemagglutination, 19%; Proteus OX-2 agglutination, 18%; and CF, 0%. Overall specificity rates were skin biopsy, 100%; hemagglutination, 99%; and agglutination of Proteus OX-2 96% and OX-19 78%. Major problems were failure to submit convalescent serum and nonspecificity of Weil-Felix titer of 1:160. Two cases illustrate the importance of skin biopsy and serologic results. Immunofluorescent examination of skin biopsies for Rickettsia rickettsii is the best procedure currently available for early diagnosis.

Adolescent↗

Mutations in coliphage p1 affecting host cell lysis.

A total of 103 amber mutants of coliphage P1 were tested for lysis of nonpermissive cells. Of these, 83 caused cell lysis at the normal lysis time and have defects in particle morphogenesis. Five amber mutants, with mutations in the same gene (gene 2), caused premature lysis and may have a defect in a lysis regulator. Fifteen amber mutants were unable to cause cell lysis. Artificially lysed cells infected with five of these mutants produced viable phage particles, and phage particles were seen in thin sections of unlysed, infected cells. However, phage production by these mutants was not continued after the normal lysis time. We conclude that the defect of these five mutants is in a lysis function. The five mutations were found to be in the same gene (designated gene 17). The remaining 10 amber mutants, whose mutations were found to be in the same gene (gene 10), were also unable to cause cell lysis. They differed from those in gene 17 in that no viable phage particles were produced from artificially lysed cells, and no phage particles were seen in thin sections of unlysed, infected cells. We conclude that the gene 10 mutants cannot synthesize late proteins, and it is possible that gene 10 may code for a regulator of late gene expression for P1.

Journal Article↗

Pathogenesis of myocarditis in Rocky Mountain spotted fever.

Because myocarditis has been noted frequently as present at necropsy in fatal Rocky Mountain spotted fever (RMSF) and ECG alterations may also accompany the disease, we studied the pathogenesis of myocarditis in RMSF. Increased heart weight in eight of nine cases and increased interstitial volume in six of nine cases suggest that myocardial edema is present. Specific immunofluorescent demonstration of Rickettsia rickettsii in myocardial capillaries, venules, and arterioles in eight of nine cases correlates well with the patchy distribution of interstitial mononuclear myocarditis and provides the pathogenic mechanism for vascular injury-induced myocardial edema. Absence of left ventricular dilation suggests that severe myocardial failure was not the apparent cause of hypotension, shock, and death in RMSF.

Adolescent↗

The rickettsial plaque. Evidence for direct cytopathic effect of Rickettsia rickettsii.

Monolayers of primary chick embryo cells were infected with Rickettsia rickettsii in a plaque assay system with 0.5 per cent agarose overlay. Plaques appeared 5 days after inoculation and were examined on day 6 by supravital staining, immunofluorescence for R. rickettsii, and electron microscopy. In all studies maintenance of the topographic integrity of the monolayer and the plaque allowed assessment of temporospatial relationships of rickettsial infection and cytopathologic changes. Plaques comprised four zones: peripheral, marginal, necrotic, and central. The cells of the peripheral zone were viable, mildly infected, and ultrastructurally normal. Cells of the marginal necrotic, and central zones exhibited a correlation between quantity of rickettsiae and presence of cytopathology. Pathologic changes included sever dilation of rough endoplasmic reticulum and necrosis. Quantitative assessment of the distribution of rickettsiae ultrastructurally showed the overwhelming predominance of cytosol location and suggested the ultrastructural sequence of events for rickettsial release from cells via lysis of cell membrane at the end of filopodia. These studies of the plaque technic provide a predictable, quantitative model for experimental investigations into mechanisms of cell injury by rickettsiae.

Animals↗

Hansenula polymorpha infection in a child with chronic granulomatous disease.

In a patient with chronic granulomatous disease of childhood documented by the nitroblue tetrazolium test, an infection of the mediastinal lymph nodes developed that was caused by Hansenula polymorpha, an ascomycetous yeast. To our knowledge, this yeast has not been previously shown to be an etiologic agent of disease in man. The diagnosis was made by growing the yeast from cultures of several biopsy specimens collected at the time of thoracotomy. Susceptibility testing showed that the yeast was sensitive to amphotericin B. Treatment with amphotericin B reversed this life-threatening episode.

Amphotericin B↗

Relapse of Legionnaires' disease in a renal transplant recipient.

We describe a 44-year-old man who recently received a cadaveric renal transplant and had a relapse of Legionnaires' disease after an appropriate course of therapy. The relapse occurred within two weeks after completion of a three-week course of therapy with erythromycin stearate. A transbronchial biopsy specimen was positive for Legionella pneumophila by direct immunofluorescence, although the Dieterle silver impregnation stain was negative. The patient responded to a repeated course of erythromycin for an additional 21 days, and no further sequelae or relapses have been noted. The importance of early rapid diagnostic modalities in the immunocompromised patient is emphasized, and the need to consider the possibility of relapse after effective therapy is warranted.

Adult↗