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Biomedical subjects

E L Howes

Publications and source records attributed to E L Howes.

At least 37 records · Page 2Linked to original sources

Evaluation of an indirect fluorescent-antibody stain for detection of Pneumocystis carinii in respiratory specimens.

Two prospective studies were undertaken to evaluate a commercial indirect fluorescent-antibody (IFA) stain for the detection of Pneumocystis carinii in respiratory specimens from individuals at risk for or with the acquired immunodeficiency syndrome. The first study compared IFA with Diff-Quik (DQ; a rapid Giemsa-like stain) for detecting P. carinii in 95 induced sputa obtained from 77 asymptomatic patients who had survived one previous episode of P. carinii pneumonia and who were being treated prophylactically with aerosolized pentamidine. Only one induced sputum specimen was found to contain P. carinii; organisms were detected by both stains. The second study compared the performance of the IFA stain versus DQ, modified toluidine blue O, and Gomori methenamine silver stains for detecting P. carinii in symptomatic individuals at risk for or with acquired immunodeficiency syndrome. Of 182 specimens examined, P. carinii was detected in 105 by one or more stains; the DQ stain detected 73 (70%), the modified toluidine blue O stain detected 75 (71%), the Gomori methenamine silver stain detected 76 (72%), and the IFA stain detected 95 (90%). The IFA stain was more sensitive (P less than 0.01) than the other traditional stains for detecting P. carinii; however, a subsequent clinical evaluation revealed that a subset of IFA-positive-only specimens were from patients whose clinical symptoms resolved without specific anti-P. carinii therapy.

Diagnostic Errors↗

Analysis of radiation failure after uveal melanoma brachytherapy.

We analyzed the number of cycling cells in the DNA synthesis phase and in mitosis in two uveal melanomas unsuccessfully treated with iodine 125 brachytherapy. In one patient, the tumor appeared to have been radioresistant, whereas the other patient had a clinically inapparent area of tumor that was not included in the tumoricidal radiation field. In the first patient, there was uniform tumor cell cycling, whereas the second patient had cycling cells predominantly in the area that did not receive optimal radiation. This gradient of cycling tumor cells in the second patient was observed with both standard histologic examination (mitoses per high-powered field) and bromodeoxyuridine staining (DNA synthesis). The bromodeoxyuridine technique was significantly more sensitive than standard histologic examination in the detection of cycling cells.

Aged↗

Histopathological evaluation of rotation sutures for involutional entropion.

Rotation sutures are a popular method of temporarily correcting involutional entropion. The permanence of the procedure depends on a fibrotic scar along the suture tracks. Sutures which create generous scars would probably produce the most satisfactory results. In this study 4-0 chromic gut, nylon, and silk sutures were evaluated in rabbit lower eyelids for their ability to create histologically demonstrable fibrous tracks. All three sutures incited inflammatory cells and fibroblastic activity with collagen formation at two and four weeks. Residual scar tracks were observed at six weeks (two weeks after suture removal) also. Human specimens showed similar types of scar formation from the sutures. It was apparent that all three sutures create fibrotic scars along their tracks sufficient to correct, at least temporarily, involutional entropion.

Animals↗

Bilateral ciliary body melanomas.

We describe a 78-year-old woman with bilateral primary ciliary body melanomas. The tumours presented 6 months apart and were treated with iridocyclectomy. Histopathological examination revealed type B spindle cell melanomas. To our knowledge this is the first reported case of bilateral ciliary body melanomas.

Aged↗

Alveolar-capillary block in patients with AIDS and Pneumocystis carinii pneumonia.

To determine the value of subdividing diffusing capacity for carbon monoxide (DL) in diagnosing and monitoring the course of Pneumocystis carinii pneumonia (PCP), we measured DL, membrane diffusing capacity (DM), and pulmonary capillary blood volume (VC) in 20 control subjects, 20 patients with a low DL (less than 75% predicted) and newly diagnosed PCP, and 16 patients with a low DL in most of whom PCP had been suspected and excluded. Ten patients with PCP were restudied approximately 60 days after treatment. When clinically indicated, lung biopsies were obtained for histologic examination. Compared with mean values in control subjects (DL = 92%, DM = 101%, and VC = 35 ml/m2), all values were decreased (p less than 0.01) in patients with PCP (DL = 58%, DM = 33%, and VC = 26 ml/m2) and in those without PCP (DL = 61%, DM = 56%, and VC = 22 ml/m2). Values of DM were significantly less (p less than 0.05) in patients with, than in those without, PCP. Analysis of lung biopsies by light and electron microscopy showed overlapping morphologic abnormalities in the 2 groups of patients. In the 10 patients with PCP restudied after successful treatment, the mean DL increased from 60 to 80% (p less than 0.0005), the DM increased from 35 to 108% (p less than 0.006), and the VC did not change. These results suggest that in contrast to most disorders in which DL is decreased, PCP causes reversible alveolar-capillary block.

Acquired Immunodeficiency Syndrome↗

Quantitation of acute experimental ocular inflammation with 111indium-leukocytes.

The cellular component of an acute ocular inflammation in rabbits was measured with autologous leukocytes exogenously labeled with 111Indium tropolonate. Inflammation was induced by intravitreal bacterial lipopolysaccharide (LPS). After 16 hr blood was removed, leukocytes separated, labeled with 111Indium tropolonate and reinjected. Three cell fractions were examined: a leukocyte rich fraction which had been prepared with Dextran; and polymorphonuclear and mononuclear leukocyte fractions which had been prepared using a discontinuous Percoll gradient. Two hours after labeled leukocytes were injected, measurements of 111Indium were made in blood, plasma, the whole eye and in ocular compartments. From these data the numbers of each leukocyte population present were estimated and compared directly to histopathologic changes. Both polymorphonuclear and mononuclear leukocytes entered ocular tissues during the 2 hr period beginning 20 hr after LPS injection. Altered ocular vascular permeability was successfully measured with 125Iodine-albumin in some of these same rabbits. Both the number and type of inflammatory cell entering ocular tissues during a set period of time of the inflammatory response could thus be measured. This technique provides an opportunity to define the relationship of leukocyte infiltration and altered ocular vascular permeability in ocular tissues during the inflammatory response.

Acute Disease↗

Ocular inflammatory effects of intravitreally-injected tumor necrosis factor.

Many of the pathophysiologic effects of bacterial endotoxin have recently been attributed to a monokine, tumor necrosis factor (TNF). The rabbit eye is extremely sensitive to locally injected endotoxin. The authors have investigated the possible contribution of TNF to ocular inflammation in a rabbit model. The intravitreal injection of 10(5) to 5 X 10(5) units of recombinant human TNF produced a sustained disruption of the blood-aqueous barrier as manifested by elevated aqueous humor protein levels. In addition, 83% of rabbits receiving this dose of TNF developed hyperemia of limbal vessels and early neovascularization of the cornea. Many developed posterior synechiae (fibrous adhesions between the iris and the lens). TNF induced only a slight cellular response in the anterior chamber. Histologic studies confirmed the presence of new vessels and demonstrated a marked mononuclear infiltrate within and beneath the epithelium of the iris and ciliary body. Lower doses of TNF produced inconsistent results. Heating TNF completely destroyed its inflammatory effects. The time course of the ocular response to TNF and the quantity of recombinant protein needed to produce consistent effects were vastly different from effects observed with interleukin-1. For example, 24 hours after an intravitreal injection, 2.2 X 10(4) ng of TNF (5 X 10(5) units) produced significantly less protein extravasation and polymorphonuclear leukocyte infiltration than 4 ng of recombinant interleukin-1. Similarly, 24 hours after intravitreal injection, 1 ng of Escherichia coli endotoxin tended to be a more potent inflammatory stimulus than this quantity of TNF. These observations indicate that the ocular pathophysiologic effects of TNF can be readily distinguished from changes induced by either endotoxin or another endotoxin induced monokine, interleukin-1.

Animals↗

Uveal melanoma with opaque media: absence of definitive diagnosis before enucleation.

It is often difficult to make a correct diagnosis of a uveal melanoma in an eye with opaque media. A patient with a blind, painful eye and opaque media was evaluated clinically and with computed axial tomography and ultrasonography. We were unable to establish the definitive diagnosis of a uveal melanoma until the eye was examined histologically. Necrotic melanomas usually present with inflammatory signs, may produce opaque media and can be difficult to diagnose with clinical and imaging studies.

Aged↗

Ocular inflammatory effects of intravitreal interleukin 1.

Locally injected endotoxin induces potent inflammatory changes in the rabbit eye. To clarify the possible role of interleukin 1 (Il-1), an endotoxin-induced monokine, in rabbit eye inflammation, we injected rabbits with recombinant Il-1 (rIl-1). Twelve and a half to 200 U of intravitreally injected rIl-1 consistently induced inflammation, which was documented using slit-lamp biomicroscopy, histologic methods, or direct quantitation of protein in the aqueous humor. Responses including a cellular infiltrate in the anterior chamber, protein extravasation, and iris vessel dilatation became evident within six hours, peaked at 24 hours, and began to recede by 48 to 72 hours after the injection. Pathologic changes primarily occurred in the anterior chamber and included edema, hemorrhage, and cellular infiltration. Locally injected corticosteroid reduced but did not prevent rIl-1-induced changes in vascular permeability. Heat-inactivated rIl-1 induced minimal changes, as determined by histologic methods, slit-lamp examination, or direct protein measurement. These data support the conclusion that Il-1 should be considered as a potential mediator of ocular inflammation.

Animals↗

Orbital optic glioma in neurofibromatosis. Magnetic resonance diagnosis of perineural arachnoidal gliomatosis.

In a patient with neurofibromatosis and orbital optic glioma, T2-weighted axial magnetic resonance images showed a fusiform area of high signal intensity with a central linear core of lower signal intensity. Computed tomographic images did not show a corresponding variation in tumor density. Histopathologic examination of the tumor revealed dense, circumferential, perineural glial proliferation. This "arachnoidal gliomatosis" is a feature of orbital optic gliomas in neurofibromatosis and, in our magnetic resonance scans, accurately corresponded with the region of high signal intensity within the tumor.

Arachnoid↗

Demonstration of herpes group virus in acute retinal necrosis syndrome.

Tissue for pathologic examination was obtained from three cases of acute retinal necrosis syndrome. Virus particles belonging to the herpesvirus family were demonstrated in retinal biopsies from two patients, one of whom was immunosuppressed. Despite removal of large biopsy specimens, the retina has remained attached for 20 months postoperatively in one case and for three months in the other. In a third patient with acquired immune deficiency syndrome, the clinical course and postmortem immunopathology were suggestive of a herpes simplex virus infection, initially affecting the retina and subsequently the optic nerves, chiasm, tracts, and central nervous system. These cases illustrate that the virus associated with the acute retinal necrosis syndrome is easily demonstrable using vitrectomy and endoretinal biopsy in the acute phase of the disease, but may be difficult to demonstrate in chronically detached atrophic retinas.

Acute Disease↗

Foreign-body giant cell reaction to liquid silicone.

Although intravitreal injections of liquid silicone have long been used in complicated retinal detachments and long-term complications such as keratopathy, glaucoma, and cataract are well-known, the effect of liquid silicone on the retina, iris, and angle structures is not as well defined. Histopathologic study of one human eye that was enucleated 20 months after liquid silicone injection showed an intraocular foreign-body giant cell reaction.

Adult↗

The effect of corticosteroids or nitrogen mustard on aqueous humor chemotactic activity induced by intravitreal endotoxin.

In rabbits intravitreal injection of endotoxin induces potent chemotactic activity for monocytes in aqueous humor. We have assessed the effect of methylprednisolone (30 mg/kg intramuscularly) or nitrogen mustard (1.75 mg/kg intravenously) on the generation of this chemotactic activity. Histologic changes, anterior chamber protein extravasation, and aqueous humor cellular infiltration were reduced by corticosteroids to a variable degree. However, even in animals with a marked reduction in protein extravasation or histologic change, chemotactic activity was substantially preserved. Similarly, nitrogen mustard induced a leukopenia without affecting the ability of endotoxin to generate chemotactic activity in aqueous humor. In contrast, corticosteroids reduced both protein extravasation and the generation of chemotactic activity induced by intravenously injected endotoxin. The results suggest that the chemotactic activity induced in the eye by intravitreal endotoxin may be locally synthesized and may be present without a substantial leukocytic infiltrate.

Animals↗

Lipopolysaccharide tolerance inhibits eye inflammation. I. Reduced immune complex or lipopolysaccharide effects.

The effect of endotoxin tolerance on ocular inflammation was studied in rabbits. A single intravenous (IV) injection of endotoxin (bacterial lipopolysaccharide [LPS]) produced a mild acute iridocyclitis. Repeated daily (five to seven days) IV injections of LPS (5 micrograms extracted from Salmonella typhimurium) led to a state of refractoriness or LPS "tolerance," and ocular inflammation was no longer produced. In contrast to controls, in rabbits tolerant to LPS, IV LPS failed to elevate prostaglandin E2, thromboxane B2, or chemotactic factors in the aqueous humor. Rabbits tolerant to LPS also resisted the increase in vascular permeability normally induced by an ocular reversed passive Arthus reaction. These results demonstrated that LPS tolerance can induce anti-inflammatory effects in the eye.

Acute Disease↗

Lipopolysaccharide tolerance inhibits eye inflammation. II. Preliminary studies on the mechanism.

The effect of endotoxin tolerance on ocular inflammation was studied in rabbits. Compared with a control group, a passive Arthus reaction in tolerant rabbits was characterized by a sharp decline in the expected increase in vascular permeability and slightly reduced leukocyte extravasation. Aqueous humor withdrawal (paracentesis) and intravitreal injection of prostaglandin E2 were also examined in lipopolysaccharide (LPS)-tolerant rabbits; in both circumstances, ocular protein exudation was decreased. These studies suggest that the prostaglandin system is particularly affected in the ocular responses of LPS-tolerant rabbits, and raise the possibility that other phenomena described in LPS tolerance may have a similar basis.

Animals↗

Endotoxin tolerance diminishes certain antiinflammatory effects of endotoxin.

Endotoxin (bacterial lipopolysaccharide, LPS) is paradoxically both inflammatory and antiinflammatory. A single intravenous injection of 100 micrograms Escherichia coli LPS markedly inhibits the inflammatory changes associated with cutaneous reversed passive Arthus (RPA) reactions in New Zealand white rabbits. Polymorphonuclear (PMN) leukocytes from LPS-treated rabbits exhibit diminished responsiveness in vitro to complement (C5) -derived peptides. Repeated injections of LPS render animals "tolerant", that is, refractory to the toxic and inflammatory effects of LPS. We examined whether tolerance would enhance the ability of LPS to inhibit inflammation not attributable to LPS. Surprisingly, as compared with rabbits receiving a single dose of LPS, tolerant rabbits demonstrated greater inflammatory changes (i.e., PMN exudation, vascular permeability) associated with RPA reactions. PMNs from LPS-tolerant rabbits responded in vitro to C5-derived peptides significantly more than PMNs from rabbits that received a single dose of LPS. We speculate that some antiinflammatory effects of LPS require the toxic or inflammatory effects of LPS itself. These observations might relate to the limited efficacy of fever therapy and the variable effects of gram-negative sepsis on functions of human PMNs.

Animals↗

Ascorbate in aqueous humor protects against myeloperoxidase-induced oxidation.

Chemotactic factors can cause polymorphonuclear leukocytes to release the contents of azurophilic granules, including the enzymes beta-glucuronidase and myeloperoxidase. In the presence of aqueous humor from the anterior chamber of the rabbit eye, the supernatant from stimulated leukocytes contains beta-glucuronidase, but myeloperoxidase is not detectable. Studies with aqueous humor and partially purified human myeloperoxidase suggest that this phenomenon is not due to a failure of enzyme release. The factor responsible for the inability to detect MPO in the assay system is heat-labile, dialyzable, and reversed by ascorbate oxidase. Comparable assay inhibition is produced by ascorbic acid at a concentration present in either human or rabbit aqueous humor. The ability of aqueous humor to protect against myeloperoxidase-induced oxidation may contribute to several diverse phenomena, including the susceptibility of the eye to Candida infection and a prolonged half-life for several inflammatory mediators in the anterior chamber.

Animals↗