Search PubMed⌕ Search

Biomedical subjects

D H Walker

Publications and source records attributed to D H Walker.

At least 181 records · Page 10Linked to original sources
PubMed1986

Lassa virus hepatitis: a study of fatal Lassa fever in humans.

In order to explore the significance of a previous observation that the most important pathologic changes in fatal Lassa fever are hepatic, we have studied postmortem liver biopsies from 19 patients with fatal Lassa fever. We observed a vigorous macrophage response to cellular damage, but we found no evidence of lymphocyte infiltration in infected hepatic tissues. Using semi-quantitative estimates of liver cell damage, we found a wide range in the severity and progression of Lassa virus hepatitis in our fatal cases. We have classified for descriptive purposes three general nosopoeitic phases: active hepatocellular injury (less than 20% necrosis), continued damage and early recovery, and mitotic activity representing hepatic recovery. We conclude that the liver goes through cellular injury, necrosis and regeneration and any or all may be present at death. In no instance was the degree of hepatic damage sufficient to implicate hepatic failure, and all three phases were represented among our cases. We conclude that the hepatitis of Lassa fever in humans is not the primary cause of death.

Hepatitis, Viral, Human↗
PubMed1986

Frequent occurrence of hepatic lesions in boutonneuse fever.

Seven consecutive Sicilian patients with boutonneuse fever but without clinical symptoms of hepatic disease underwent hepatic biopsy and had similar hepatic lesions. Foci of hepatocellular necrosis were infiltrated with predominantly mononuclear leukocytes. No intact Rickettsia conorii were identified in the tissues by immunofluorescence. The apparent high frequency of viscerotropism in boutonneuse fever conforms to the recent observations of severe illness in what had often been described previously as a benign rickettsiosis.

Adult↗
PubMed1985

Pulmonary pathology of Rocky Mountain spotted fever (RMSF) in children.

Despite infrequent respiratory symptoms, histopathologic changes were identified in the lungs of 15 of 16 children dying of Rocky Mountain spotted fever (RMSF). Gross examination demonstrated increased lung weight, edema, congestion, focal hemorrhage, and bronchopneumonia in a few cases. Paraffin sections were stained with hematoxylin and eosin and phosphotungstic acid-hematoxylin, and available blocks were examined by direct immunofluoresence for Rickettsia rickettsii. Cases and controls matched for age and sex were randomized and examined blindly for pathologic changes. In addition, morphometric measurements of mean alveolar septal thickness were made in each case. The histopathologic findings include (1) diffuse interstitial mononuclear (lymphocyte and macrophage) inflammatory infiltrate in 15/16 cases of RMSF (5/10 controls), (2) pulmonary edema and intraalveolar hemorrhage in 11/16 cases of RMSF (2/10 controls), and (3) vasculitis of small pulmonary venules and arterioles in 5/16 RMSF cases (0/10 controls). Rickettsia rickettsii were identified in 4/8 RMSF cases by direct fluorescent antibody technique. Although pulmonary disease is not always clinically apparent in children with RMSF, involvement of the pulmonary microcirculation is a frequent event in fatal cases and may contribute to the development of non-cardiogenic pulmonary edema.

Adolescent↗
PubMed1985

Correlation of the distribution of Rickettsia conorii, microscopic lesions, and clinical features in South African tick bite fever.

Three South African patients with severe Rickettsia conorii infection had complicated courses of illness with 2 fatal cases and 1 with gangrene of multiple digits. Immunofluorescent organisms of R. conorii were demonstrated in vascular endothelium of brain, leptomeninges, renal glomerular arterioles and capillaries, renal arteries and veins, myocardial capillaries and arteries, pulmonary alveolar capillaries, pancreatic septa, splenic arterioles, and dermis. Rickettsiae were also observed in hepatic sinusoidal lining cells, splenic and lymph node macrophages, and the blood vessels of the partially viable zone of the amputated digits. Pathologic lesions included cerebral and cerebellar perivascular mononuclear leukocytes, mild mononuclear leptomeningitis, glomerular arteriolitis, vascular and perivascular mononuclear cell-rich inflammatory foci in the kidney, pancreas, skin, and myocardium, hepatocellular necrosis, and pulmonary edema. The sites of lesions and rickettsiae showed strong topographical correlation. Thrombi and hemorrhage occurred in a minority of the sites of vascular injury. Rickettsiae were the apparent direct cause of meningoencephalitis, peripheral gangrene, and other foci of vascular injury. Fatal R. conorii infection with disseminated organ involvement emphasizes the pathogenic potential of this disease.

Aged↗
PubMed1985

Kinetic study of platelets and fibrinogen in Lassa virus-infected monkeys and early pathologic events in Mopeia virus-infected monkeys.

The rhesus monkey, an established model of Lassa fever, was used to study hematologic and hemostatic aspects of Lassa fever and whether Mopeia (also known as Mozambique) virus induces any cellular damage in this model. Six days after subcutaneous injection of 10(3.48) plaque forming units (PFU) of Lassa virus (Josiah strain) one group of monkeys received an intravenous injection of 111In-labeled allogeneic platelets and another group received 125I-labeled alogeneic fibrinogen. Lassa virus-infected monkeys developed a severe clinical illness with high viremia and typical pathology. Lassa antigen was found in most tissues using a Lassa nucleocapsid-specific monoclonal antibody. Platelet counts remained within normal limits. Platelet and fibrinogen kinetics were similar in infected and control animals. Hematologic and hemostatic changes indicate that disseminated intravascular coagulation plays no role in this model of Lassa fever. Levels of plasma fibronectin were reduced in Lassa-infected monkeys. Mopeia virus-infected monkeys were normothemic, aviremic, and there was no detection of Mopeia antigen in any tissues using polyclonal or monoclonal antibodies. Mopeia virus was recovered from the spleen of one monkey. Mopeia virus was associated with hepatocellular and renal tubular damage.

Animals↗
PubMed1985

Canine Rocky Mountain spotted fever: a kennel epizootic.

Within a period of 5 consecutive days after the initial observation of illness was made, 7 of 12 Siberian Husky dogs developed clinical signs of Rickettsia rickettsii infection. One dog died and was necropsied. Clinical signs of infection consisted of lethargy, anorexia, ocular and nasal discharges, and neurologic disorder (incoordination and rolling). Scleral blood vessel injection, fever, lymphadenomegaly, splenomegaly, and increased bronchovesicular lung sounds were prominent findings. Clinical laboratory test results identified decreased platelet numbers, variable neutrophil counts, increased serum alkaline phosphatase activity, hyponatremia, hypokalemia, and bilirubinuria. Diagnosis of Rocky Mountain spotted fever was confirmed by serologic evaluation of acute and convalescent sera, using the micro-immunofluorescence technique, and R rickettsii antigen was determined by demonstration of intracellular rickettsial organisms in vascular endothelial cells of brain and lung (stained with carbol-basic fuchsin and aqueous malachite green) and by demonstration of spotted fever-group rickettsiae in tissues by direct fluorescent antibody technique. Near-simultaneous naturally occurring tick-borne infection of 7 dogs with R rickettsii documents an unreported occurrence.

Animals↗
PubMed1985

Rocky Mountain spotted fever mimicking acute cholecystitis.

Rocky Mountain spotted fever can present with predominantly abdominal symptoms including nausea, vomiting, diarrhea, and abdominal pain. Two elderly patients presented with an acute febrile illness and abdominal symptoms. Rash was not present initially. Workup disclosed cholelithiasis in one, and a thickened gallbladder wall surrounded by a sonolucent zone suggesting a pericholecystic abscess was found by ultrasonography in the other. Both patients underwent emergency laparotomy, with cholecystectomy in both and appendectomy in one. Both patients died several days postoperatively. Pathologic specimens reviewed later showed that multiple blood vessels of the gallbladder and the appendix were infected with Rickettsia rickettsii, and there was focal vascular thrombosis and hemorrhage. These documented direct rickettsial infections and lesions in the blood vessels of abdominal viscera suggest the basis for the abdominal symptoms in Rocky Mountain spotted fever.

Acute Disease↗
PubMed1984

Morphological characteristics of a unique intracytoplasmic neuronal inclusion body.

Unique intracytoplasmic inclusion bodies unaccompanied by a clinically apparent neurologic disease were found in the neurons of the hippocampus, subiculum, and mammillary body of a man who died suddenly, presumably of cardiac disease. The eosinophilic inclusions were round and often targetoid , with a central core that had the staining characteristics of RNA. Ultrastructurally, the inclusions were mainly composed of osmiophilic granular material. Rabies viral antigen was not detected by immunofluorescence, and heavy metals were not detected by energy dispersive spectrometry. These neuronal inclusions should be distinguished from Negri bodies.

Brain Diseases↗
PubMed1984

Rocky Mountain spotted fever vaccine: a regional need.

Because the killed Rickettsia vaccines have failed to provide protection against Rocky Mountain spotted fever, we approached the problem of protective immunity to Rickettsia rickettsii with a closely related, live, less pathogenic spotted fever Rickettsia. Guinea pigs vaccinated with R conorii produced antibodies to spotted fever group rickettsiae and did not have fever or other signs of illness after challenge with R rickettsii. A vaccine against Rocky Mountain spotted fever would be useful in some medical practices in the southeastern United States because of the life-threatening nature of the disease, including the possibility of a fulminant course and the frequent difficulty in diagnosis. Further studies should be pursued toward the goal of developing an effective vaccine against Rocky Mountain spotted fever.

Animals↗
PubMed1984

Effect of synthetic protease inhibitors of the amidine type on cell injury by Rickettsia rickettsii.

To evaluate the importance of proteolytic activity in the pathogenesis of cell injury by Rickettsia rickettsii, a series of four aromatic amidine inhibitors of trypsin-like proteases were introduced into the plaque model. The compounds were shown to be active toward plaque reduction with their order of effectiveness parallel to their antitrypsin activity. One of the compounds, bis(5-amidino-2-benzimidazolyl)-methane, at a concentration of 10(-5) M demonstrated complete inhibition of plaque formation on day 6. Bis(5-amidino-2-benzimidazolyl)methane at the same concentration reduced cell injury even when added to the system after 72 h of rickettsial infection. The reduction in morbidity in guinea pigs experimentally infected with R. rickettsii and treated with bis(5-amidino-2-benzimidazolyl)methane as compared with morbidity in infected, untreated animals, comprised delay in the onset of fever and slightly fewer febrile animals. Because bis(5-amidino-2-benzimidazolyl)methane had no effect on phospholipase A2, the enzyme activity associated with penetration-induced cell injury, it is likely that a trypsin-like protease also plays an essential role either in the physiology of R. rickettsii or as its pathogenic mechanism.

Amidines↗
PubMed1984

Production and characterization of monoclonal antibodies to Rickettsia rickettsii.

Five mouse ascitic fluids (MAFs) containing monoclonal antibody to Rickettsia rickettsii were produced from three original fusions by murine hybridoma technology. The five MAFs were fractionated and purified; each contained monoclonal antibody of the immunoglobulin G2a subclass. Each monoclonal antibody-containing MAF was titrated by indirect immunofluorescence against three R. rickettsii isolates from humans and four other spotted fever group rickettsiae. Each MAF was also titrated in the complement fixation, latex agglutination, microagglutination, and indirect hemagglutination tests. Two of the MAFs were examined for their ability to prevent fever and rickettsemia in susceptible guinea pigs after a 1:100 dilution of each was mixed with viable R. rickettsii, and all five MAFs were titrated in the mouse toxicity phenomenon assay. All MAFs had high indirect immunofluorescence titers to the three strains of R. rickettsii (1:200,000 to 1:800,000), reduced indirect immunofluorescence titers to R. montana, and were nonreactive with R. akari, R. sibirica, and R. conorii. Each MAF was able to fix complement in the presence of spotted fever group antigen reagent and agglutinate a suspension of purified R. rickettsii, and each was negative in both the latex agglutination and the indirect hemagglutination tests. The two MAFs which were tested proved to be capable of preventing rickettsemia and death in guinea pigs, and each MAF was able to prevent death in mice at dilutions ranging from 1:40 to 1:80.

Animals↗
PubMed1984

Demonstration of spotted fever group rickettsiae in the tache noire of a healthy person in Sicily.

A human case of rickettsial infection occurred in Sicily following tick bite. The patient did not have fever, the typical nodular rash, or other symptoms of illness other than development of a tache noire containing spotted fever group rickettsiae, which were demonstrated by immunofluorescence. A high titer of antibodies of the IgG class suggests that the patient may have had previous exposure to Rickettsia conorii or a related spotted fever group rickettsia. An anamnestic response may be hypothesized to have conferred partial immunity, with resulting containment of rickettsiae at the site of inoculation.

Antibodies, Bacterial↗
PubMed1984

Injury restricted to cells infected with spotted fever group rickettsiae in parabiotic chambers.

One chamber of paired parabiotic chambers separated by 0.2 micron poresized membrane filters which prevented passage of rickettsiae were infected with either Rickettsia rickettsii or R. conorii. Infected VERO cell monolayers underwent necrosis. Uninfected monolayers in adjoining chambers which shared the same extracellular milieu including soluble rickettsial products did not undergo necrosis.

Animals↗
PubMed1984

Infection of genetically immunodeficient mice with Rickettsia conorii.

In order to determine the definitive importance of T- and B-lymphocytes in immunity to Rickettsia conorii, mice genetically deficient in T-cells, B-cells, or both T- and B-cells were infected experimentally. T-lymphocytes rather than humoral antibodies were crucial to rickettsial clearance and a reduced mortality rate. Mice incapable of an antibody response to polysaccharide capsular antigens effectively controlled rickettsial infection with no mortality. In contrast, nude mice produced antibody to thymus-independent antigens early in the course of infection, yet experienced severe rickettsial infection resulting in deaths. The observed hepatic lesions are similar to those of boutonneuse fever. This model offers the opportunity to investigate rickettsial immune mechanisms and hepatic injury.

Animals↗
PubMed1984

Rocky Mountain spotted fever. Gastrointestinal and pancreatic lesions and rickettsial infection.

Recent clinical studies have shown a high incidence of nausea, vomiting, diarrhea, and abdominal pain in Rocky Mountain spotted fever (RMSF), and case reports have documented rickettsial infection and vascular injury in the small intestine, appendix, and gallbladder. To determine the incidence and distribution of Rickettsia rickettsii and rickettsial lesions that might be the basis for these clinical manifestations of RMSF, tissues that were available from the stomach, small intestine, colon, and pancreas in fatal cases of RMSF were examined. Lesions were identified in pancreatic tissue in 91% of cases and in tissue obtained from the stomach, small intestine, and colon in all cases. Most tissues were judged to be only moderately injured. Organisms of R rickettsii were demonstrated by immunofluorescence in 14 (50%) of 28 cases and, when identified, correlated topographically with the location of vascular injury. These observations support the concept of rickettsial vascular injury of the gastrointestinal (GI) tract and pancreas leading to GI signs and symptoms in RMSF.

Abdomen↗