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Biomedical subjects

A M Marty

Publications and source records attributed to A M Marty.

17 recordsLinked to original sources

Neoplastic change in Onchocerca volvulus and its relation to ivermectin treatment.

A pleomorphic neoplasm (PN) is described from sections of Onchocerca volvulus worms in nodules excised from Cameroonian patients. PN is confined to older, non-fecund, female worms, and those classed as moribund/dead. It is mainly composed of small, roundish, basophilic cells of diverse sizes, often forming a 'rosette' pattern around amorphous eosinophilic centres. The cells have a high nuclear/cytoplasmic ratio and up to 2-3 mitoses/high-power field; some become grossly enlarged, highly polymorphic and contain large, irregular blocks of chromatin. The eukaryotic PN cells first appear posteriorly in the pseudocoelom, probably from ovarian cells; they spread anteriorly, invading or compressing the uteri. Ivermectin treatment increased the prevalence PN from 3.7% of 1422 female worms in 637 patients before treatment to 17.5% of 1134 worms in 511 patients after 3 years treatment. Ivermectin at 400-800 microg/kg annually, or at 150 microg/kg or 400-800 microg/kg 3-monthly, over 3 years, did not increase the PN prevalence significantly, as compared with standard doses of 150 microg/kg annually. In other small series of African patients, PN prevalence increased in worms 2, 4, 6 and 10 months after ivermectin treatment; but there was no increase after treatment with amocarzine, albendazole or diethylcarbamazine and suramin. PN may partly account for the increased macrofilaricidal action of ivermectin on female O. volvulus in patients treated for 3 years at 3-monthly intervals.

Adult↗

Recent challenges in infectious diseases. Biological pathogens as weapons and emerging endemic threats.

This article reviews emerging and re-emerging infectious diseases and provides insights regarding the evolution of our understanding of natural diseases and how that knowledge impacts the development of plans and methods for defending against the deliberate use of biological agents. Also discussed are forensic and legal issues for the pathologist concerning agents of biological terrorism and biological warfare, the concept of chain of custody, transport, storage, and biosafety levels. It defines the importance of the pathologist in managing the threat posed by biological weapons.

Biological Warfare↗

History of the development and use of biological weapons.

The United States began its BW program based on intelligence information and a very thorough evaluation of that information by a panel of scientists, engineers, medical personnel from a variety of areas including the military, other government agencies, industry, and the academic community. Initial efforts were directed toward defense against BW, but it soon became clear defense required a knowledge of offensive capabilities. The initial offensive studies started with a definition of what infectious organisms were available, how they could grow in quantities to support a munitions program, what kind of facilities were required, and where they could be positioned. Further studies were then initiated to design and evaluate testing sites and methodologies to evaluate the weapons. During all of these phases, concurrent medical and safety programs were studied, emphasized, and implemented. These studies resulted in the development of a number of vaccines, toxoids, treatments, therapies, and facility personnel management. The US program had one of the lowest, if not the lowest, personnel lost time because of personnel infections. The overall conclusion was that BW, offensive and defensive, was possible, and efficiencies could be obtained. The work accomplished by this group of very dedicated military and civilian personnel at military installations, universities, research institutes, and industrial organizations presented truly a combined operation with numerous achievements. Many of the detailed achievements were published in the open scientific, peer-reviewed journals, and many patents were obtained. The current defensive program is breaking new scientific ground and there is evidence indicating that very rapid detection and identification of BW agents is possible and will be instrumented.

Biological Warfare↗

Clinicopathologic aspects of bacterial agents.

Bacteria were the first organisms recognized for their potential as agents of bioaggression and the possibility of their use by a terrorist or rogue nation is considered a significant threat. Five of the more likely agents (anthrax, plague, tularemia, Q fever, and brucellosis) are reviewed with emphasis on their epidemiology, clinical presentation, diagnosis, and pathology. Particular emphasis is given to the presentation of the diseases as they may appear after use in a biowarfare scenario.

Bacterial Infections↗

Inflammation is a component of neurodegeneration in response to Venezuelan equine encephalitis virus infection in mice.

Infection with the mosquito-transmitted Venezuelan equine encephalitis virus (VEE) causes an acute systemic febrile illness followed by meningoencephalitis. In this communication we characterize the cytokine profile induced in the central nervous system (CNS) in response to virulent or attenuated strains of VEE using RNase Protection Assays. Virulent VEE causes an upregulation of multiple pro-inflammatory genes including inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-alpha). To determine if iNOS and TNF-alpha contribute to the neuropathogenesis of VEE infection, iNOS and TNF receptor knockout mice were used in VEE mortality studies and exhibited extended survival times. Finally, CNS tissue sections labeled for VEE antigen, and adjacent sections double-labeled for an astrocyte marker and apoptosis, revealed that apoptosis of neurons occurs not only in areas of the brain positive for VEE-antigen, but also in areas of astrogliosis. These findings suggest that the inflammatory response, which is in part mediated by iNOS and TNF-alpha, may contribute to neurodegeneration following encephalitic virus infection.

Animals↗

Increased macrophage infiltration of gastric mucosa in Helicobacter pylori-infected children.

The purpose of the study was to quantify gastric mucosal macrophages and define their association with the histopathologic features of stomach biopsies obtained from Helicobacter pylori-infected and uninfected children. Endoscopically obtained gastric biopsies from symptomatic children were independently evaluated by two groups of pathologists. Thirty children were evaluated; 14 were H. pylori-infected. H. pylori positivity was determined by hematoxylin and eosin (H&E), Giemsa, Warthin-Starry and an H. pylori-specific immunoperoxidase stain. A macrophage-specific, KP-1, immunoperoxidase stain was used to quantify positive cells. Inflammatory cell infiltrates were graded by severity with scores of mild to severe. Increased numbers of gastric mucosal macrophages were observed in biopsies of H. pylori-infected versus uninfected children (P < 0.05) and correlated with gastritis severity. The role of this inflammatory cell the in persistence of gastric mucosal inflammation in H. pylori infection warrants further study to develop targeted immunotherapeutic strategies.

Adolescent↗

Distinguishing lipid pseudomembranes from larval cestodes by morphologic and histochemical means.

BACKGROUND: Contributors regularly submit specimens to our institute and suggest a diagnosis of cestode infection, but the structures in question are actually lipomembranous changes that produce lipid pseudomembranes. This required a reproducible method to distinguish lipid pseudomembranes from body walls of cestodes. METHODS: We describe and compare the morphologic and histochemical features of specimens from 20 patients. Nine specimens represented lipid pseudomembranes, and 11 represented one of the following five entities: cysticercus, coenurus, sparganum, hydatid of Echinococcus granulosus, or metastatic solid-bodied cyclophyllidean (possibly cysticercoid) larval cestodes. Specimens were stained with hematoxylin-eosin, Gomori's methenamine-silver, and 72-hour oil red O. Nine patients with cestodes, and all with lipid pseudomembranes, presented with subcutaneous lesions. RESULTS: In all specimens, oil red O provided marked contrast between lipid pseudomembranes and surrounding tissue, but focal or minimal contrast between larval cestodes and surrounding tissue. Unlike hematoxylin-eosin, Gomori's methenamine-silver stain produced distinctly different staining patterns in larval cestodes and lipid pseudomembranes. CONCLUSIONS: This technique readily permitted a simple, reproducible, and accurate distinction between lipid pseudomembranes and cestode body walls and distinguished between body walls of different cestodes.

Animals↗

Isolation and modulation of growth of a colonization-impaired strain of Enterobacter cloacae in cucumber spermosphere.

Enterobacter cloacae A-46 was isolated for use in an environmental containment strategy for genetically modified derivative strains with enhanced biocontrol activity. The population of E. cloacae A-46, a transposon mutant of the plant-beneficial bacterium E. cloacae 501R3, increased 10-fold (significant increase at P < or = 0.05) in cucumber spermosphere when applied to cucumber seeds along with casamino acids. In contrast, strain A-46 was incapable of proliferation in cucumber spermosphere in the absence of casamino acids. Populations of strain A-46 also failed to increase in corn, cowpea, sunflower, and wheat spermospheres in the absence of casamino acids, while populations of strain 501R3 increased 3162-, 512-, 1698-, and 93-fold, respectively. In addition, the persistence of strain A-46 in corn, cucumber, and sunflower rhizospheres and in natural soil was greatly reduced compared with the parental strain 501R3.

Cucumis sativus↗

Ehrlichiosis mimicking thrombotic thrombocytopenic purpura. Case report and pathological correlation.

Human ehrlichiosis is a tick-borne zoonosis caused by the newly described human hematotropic rickettsiae, Ehrlichia chaffeensis. The pathology and pathogenesis of human ehrlichiosis have not been adequately studied. Even with immunoperoxidase, the only previously known method to detect these organisms in tissue, ehrlichae are difficult or impossible to identify. This led many investigators to speculate that the pathogenesis of ehrlichiosis was not caused directly by the organism but could be caused by host-mediated injury. In this case study, a patient presented with rapidly progressive central nervous system symptoms and severe thrombocytopenia, prompting a presumptive diagnosis of thrombotic thrombocytopenic purpura (TTP). Despite corticosteroids, and later, antibiotics, the patient rapidly deteriorated and died. Postmortem examination showed hemorrhages in multiple organs and mononuclear inclusions of infection with a monocytic ehrlichia. Other findings included widespread lymphohistiocytic perivascular infiltrates, focal hepatic necroses, interstitial pneumonitis, interstitial nephritis, mononuclear phagocyte invasion and proliferation in splenic, liver, and bone marrow, and hemophagocytosis. The diagnosis was proven by serology, immunohistology with both polyclonal and monoclonal anti E chaffeensis, and polymerase chain reaction on paraffin-embedded tissues using E chaffeensis-specific oligonucleotide primers. The presence of numerous ehrlichia with notable tissue and cellular injury but without a marked host response indicate that unlike other cases of documented human ehrlichiosis, this patient died after significant direct ehrlichia-mediated injury, and that immune mechanisms initiated after ehrlichiosis played little if any role in the pathogenesis.

Aged↗

Unusual infections in humans.

Nine cases of unusual infections in humans are presented. In each case, we present the clinical history, histopathologic changes (if indicated), morphologic features of the causative organism, diagnosis, discussion, differential diagnosis, therapy, and current literature. All of the cases are illustrated with pertinent photographs. The nine cases are as follows: (i) acanthocephaliasis, the first acquired human infection by Moniliformis moniliformis in the United States; (ii) dipylidiasis, an uncommon infection caused by the dog tapeworm, Dipylidium caninum; (iii) granulomatous amebic encephalitis, caused by the recently identified leptomyxid group of amebae; (iv) schistosomiasis, a dual infection of the urinary bladder with the rare presentation of both adult worms and eggs of Schistosoma haematobium and Schistosoma mansoni in tissue sections; (v) syphilitic gastritis, an uncommon presentation of Treponema pallidum infection, in a patient with an additional incidental infection by Helicobacter pylori; (vi) microsporidiosis, the only infection caused by a Pleistophora sp. in humans; (vii) sporotrichosis, a rare disseminated infection caused by Sporothrix schenckii with numerous yeast cells in the scrotum; (viii) angiostrongyliasis, the first and only infection caused by Angiostrongylus costaricensis acquired in either Puerto Rico or the United States; and (ix) botryomycosis of the skin and subcutaneous tissue, caused by gram-positive cocci with an unusually large number of granules.

Adult↗

Current concepts in the pathogenesis of leprosy. Clinical, pathological, immunological and chemotherapeutic aspects.

In recent years there have been notable advances in the laboratory investigation and field management of leprosy. Progress, however, continues to be hindered by the lack of efficient methods for early diagnosis and implementation of control and treatment measures. Diagnosis is still made on the same principles as a century ago (clinical and histopathological findings), and only 1 in 3 known patients worldwide receives optimal chemotherapy. In 1988, nearly 1 in 10 newly diagnosed patients already had debilitating deformities. Contributing factors are operational, administrative and financial difficulties in implementing multidrug therapeutic regimens, inadequately trained personnel, and lack of priority and political commitment to leprosy control. The formulation and implementation of multidrug therapy is the most important development in leprosy in the past 10 years. Dapsone monotherapy was the mainstay for treatment and control for approximately 40 years, but secondary dapsone-resistant strains, first noted in 1964, now infect as many as 50% of all new patients. Multidrug regimens recommended by the WHO consist of various combinations of therapy using dapsone, rifampicin, clofazimine and a thionamide. Duration of therapy is limited to 6 months for paucibacillary and 2 years or more for multibacillary patients; relapse rates thus far are low. The average cost of treatment worldwide, including the cost of drugs, is estimated at $US150 per patient. The recent annual drop of nearly 8% in newly registered patients may be due to the implementation of these therapeutic regimens. Newer drugs that may be introduced into these regimens include fluoroquinolones, minocycline and clarithromycin. While knowledge of the microbiology of the leprosy bacillus and host response has advanced remarkably, there is little improvement in the understanding or amelioration of social aspects of leprosy. Better treatment and control reduces the stigma, but improvements in the attitudes of patients and society towards leprosy are as important as advances in medical science in achieving ultimate eradication of the disease.

Acquired Immunodeficiency Syndrome↗

Histopathology and doxycycline treatment in a previously healthy non-AIDS patient systemically infected by Mycoplasma fermentans (incognitus strain).

The newly recognized human pathogenic mycoplasma M. fermentans (incognitus strain) causes a fatal systemic infection in experimental monkeys, infects patients with AIDS, and apparently is associated with a fatal disease in previously healthy non-AIDS patients. An apparently immunocompetent male who lacked evidence of HIV infection developed fever, malaise, progressive weight loss, and diarrhea and had extensive tissue necrosis involving liver and spleen. M. fermentans (incognitus strain) was centered at the advancing margins of these necrotizing lesions. Following the treatment of 300 mg doxycycline per day for 6 weeks, he recovered fully. He has no fever or diarrhea, and his abnormal liver function tests have returned to normal. He regained all lost strength and 14 kg of lost weight and has remained disease free for more than 1 year.

Acquired Immunodeficiency Syndrome↗

North American paragonimiasis. A case report.

BACKGROUND: Paragonimiasis is a parasitic infection with a predilection for pulmonary involvement. Paragonimus species occur throughout the world and exist in nature in a snail-crustacean-mammalian life cycle. Human disease is most frequently encountered in cultures that ingest raw or undercooked crustaceans. North American paragonimiasis, caused by an endemic Paragonimus species, Paragonimus kellicotti, predominantly causes disease in carnivorous and omnivorous animals but may cause human disease if the intermediate host, the crayfish, is ingested raw or undercooked. CASE: A previously healthy, 21-year-old male was infected with P kellicotti and developed parasitic hemoptysis. The disease was contracted through the ingestion of local, undercooked crayfish. Diagnosis was established through the morphologic examination of eggs in the cytologic preparation of bronchioalveolar lavage fluid. The patient was successfully treated with praziquantel and recovered without incident. CONCLUSION: Paragonimiasis is a cause of parasitic hemoptysis worldwide. Paragonimiasis is infrequently encountered in North America and is usually not considered in the differential diagnosis of hemoptysis unless specific risk factors are known. The cytologist or cytopathologist, therefore, may be the first to encounter the diagnostic eggs and should be familiar with this disease.

Adult↗