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Biomedical subjects

M A Gordon

Publications and source records attributed to M A Gordon.

At least 37 records · Page 2Linked to original sources

Three-dimensional computerized reconstruction. Illustration of incremental articular cartilage thinning.

RATIONALE AND OBJECTIVES: The authors have addressed the ability of magnetic resonance (MR) imaging to resolve incremental thinning of articular cartilage by assessment of three-dimensional (3-D) and two-dimensional (2-D) representations. METHODS: Using a porcine knee model, sequential cartilage shavings were characterized using a 3-D fat suppressed spoiled gradient-echo (SPGR) MR imaging protocol that provided good contrast between high-signal articular cartilage and lower signal surrounding tissues. Lesion dimensional measurements were made on both MR images and 3-D computerized reconstructions. Volumes of cartilage removed were approximately 0.06 mL. RESULTS: Incremental articular cartilage thinning typically was apparent on 3-D reconstructed images. Three-dimensional articular cartilage reconstructions were effective in depicting location and orientation of shaved cartilage regions. Average percent error associated with length and with measurements based on 2-D MR images was approximately 19% for observer 1 and 33% for observer 2 when compared with direct measurements of the shaved cartilage. Average percent error of thickness measurements based on 2-D MR was approximately 21% for observer 1 and 37% for observer 2. Overall average errors associated with length, width, and thickness measurements were approximately 25%. CONCLUSIONS: Incremental thinning of articular cartilage can be tracked qualitatively and quantitatively using 3-D computerized reconstructions and 2-D MR images. Errors associated with the quantitative measurements can be attributed to limitations of measurement methods and intrinsic limitation of MR resolution.

Animals↗

Analysis of pallidotomy lesion positions using three-dimensional reconstruction of pallidal lesions, the basal ganglia, and the optic tract.

OBJECTIVE: To assess the position of radiofrequency pallidotomy lesions placed using microelectrode stimulation and cellular recordings in relation to a stereotactically defined starting point. Radiofrequency lesion locations were also evaluated in relation to the putamen, posterior limb of the internal capsule, and optic tract. METHODS: Magnetic resonance images obtained from 23 patients with Parkinson's disease who underwent pallidotomy at the University of Kansas Medical Center were analyzed. Using computerized techniques, lesion positions in relation to the midcommissural point and a hypothetical starting point were determined. Data segmentation and three-dimensional reconstruction of pallidal lesions, the internal capsule, and the optic tract allowed assessment of lesion position in relation to internal anatomy. Clinical outcome of pallidotomy was assessed using both the Unified Parkinson's Disease Rating Scale and the Dementia Rating Scale. RESULTS: Pallidal lesions were usually placed anterior and dorsal to the stereotactically defined starting point. The position of pallidal lesions in the men were observed, in four trials, to be significantly more dorsal than the lesions in the women. The outer zone of the lesion was usually adjacent to the internal capsule and the putamen and relatively close to the optic tract. The inner zone of the lesion was usually several millimeters removed from anatomic boundaries of the putamen, internal capsule, and optic tract. Patients achieved favorable outcomes, with reduced dyskinesias and "off" time and improvement of their Parkinsonian symptoms, as evidenced by clinical assessment, the Unified Parkinson's Disease Rating Scale, and the Dementia Rating Scale. CONCLUSION: Microelectrode stimulation and cellular recordings usually led to a final pallidotomy lesion position that deviated from the stereotactically defined starting point. The pallidotomy lesions in the men were observed to be more dorsal than the lesions in the women. Clinical outcomes were not correlated with either lesion location relative to the starting point or distances between the pallidal lesion and the putamen, internal capsule, or optic tract. Kinesthetically responsive cells may be localized generally more anterior and dorsal to the starting point (within the globus pallidus) and may be grouped variably from patient to patient in relation to other basal ganglia structures. Although the primary lesion site is most likely within the sensorimotor region of the globus pallidus internus, the more dorsal locations of responsive cell groups may indicate that some lesion sites may be localized within the globus pallidus externus.

Aged↗

Case report: pathomorphology of an experimental disseminated Aspergillus fumigatus infection in rabbits.

In following a formerly successful protocol designed to produce antibodies to A. fumigatus (Fres) we observed a disseminated, lethal fungal infection in healthy, specific pathogen-free (SPF) rabbits. The pathomorphological findings included multiple miliary to avenaceous whitish nodules in the livers and kidneys, mycotic mesencephalitis, nephritis, hepatitis, myocarditis, hemorrhagic enteritis, and splenitis. The hyphae were surrounded by necrosis, which also occurred in the liver without the hyphae. Comparative gas chromatographic and metabolic investigations on this strain and some environmental A. fumigatus strains showed significant differences. The findings are discussed with particular reference to the pathogenicity of A. fumigatus.

Animals↗

Textural parameters based on the Spatial Gray Level Dependence Method applied to melanocytic nevi.

The purpose of this study is to evaluate the Spatial Gray Level Dependence Method (SGLDM) of texture analysis with respect to its ability to discriminate between melanocytic nevi and normal skin. Thirteen textural features based on the SGLDM were evaluated with respect to their relative sensitivities to both texture and tone. Ten features were found to be more sensitive to texture than tone and were selected for further study. Twenty-four digitized images of benign melanocytic nevi were obtained from six volunteers. Ten textural features were analyzed for each nevus and for surrounding sections of normal skin. Of these 10 features, 8 features can distinguish between textural properties of melanocytic nevi and surrounding skin.

Humans↗

Effect of pentoxifylline on the course of systemic Candida albicans infection in mice.

Pentoxifylline can decrease the production of tumour necrosis factor alpha (TNF alpha) by endotoxin-stimulated macrophages and may improve survival in animals with overwhelming bacterial sepsis. In this study various doses of pentoxifylline were administered to mice with systemic Candida albicans infection to determine its effect on serum TNF alpha levels, organ fungal burden, and host survival. Intraperitoneal injections of pentoxifylline at 20 mg/kg every 8 h did not affect these endpoints. However, fungal counts were significantly higher in kidneys of animals that received 30 and 60 mg/kg of pentoxifylline every 8 h when compared to controls. Injection of 60 mg/kg of pentoxifylline at 8 h intervals also significantly shortened mean survival from 5.8 to 3.8 days (P = 0.01). Pentoxifylline did not affect peripheral WBC counts, serum TNF alpha and interleukin-6 levels, or the density of neutrophils in tissues. In vitro, pentoxifylline decreased the production of TNF alpha by C. albicans-stimulated macrophages in a dose-dependent manner, but only at concentrations greater than 100 mg/L. In contrast, pentoxifylline suppressed TNF alpha production by endotoxin-stimulated macrophages at concentrations as low as 10 mg/L. Thus, higher doses of pentoxifylline are detrimental in systemic C. albicans infection. However, the detrimental effect is not mediated by alterations in serum TNF alpha or interleukin-6 levels or the aggregation of neutrophils in tissues.

Animals↗

Right ventricular function during revision total hip arthroplasty.

Total hip arthroplasty (THA) is associated with pulmonary embolization of cement-bone marrow debris leading to cardiopulmonary complications including cardiac arrest. These complications are more prevalent during revision THA. This report assessed right ventricular function using a right ventricular ejection fraction pulmonary artery catheter (RVEF) and transesophageal echocardiography (TEE) in 18 patients undergoing revision THA. During femoral prosthesis insertion, all patients exhibited hemodynamic changes, but most of these were small and clinically insignificant. Four patients demonstrated a decrease in RVEF > or = 10% and an increase in mean pulmonary artery pressure > or = 10 mm Hg, requiring physician intervention. Two of these patients exhibited signs of pulmonary embolization postoperatively. All patients studied by TEE had detectable intracardiac emboli during femoral arthroplasty. The acute decreases in RVEF and increases in mean pulmonary artery pressures during hip arthroplasty, suggest a role for the embolization of bone marrow debris in the development of the "bone cement implantation syndrome."

Adult↗

Analysis of three-dimensional computerized representations of articular cartilage lesions.

RATIONALE AND OBJECTIVES: The authors assess the accuracy of three-dimensional (3D) computer representations based on magnetic resonance images of articular cartilage lesions, using actual cartilage lesions as reference standards. METHODS: Grade 2 and grade 3 articular lesions were created on articular surfaces of five porcine knee joints. The knees were then imaged using 3D fat-suppressed SPGR acquisition at four different slice thicknesses. Magnetic resonance imaging data sets were transferred to a computer workstation for image processing and 3D reconstruction. Lesion dimensions (length, width, and depth) based on the 3D reconstructed image were compared with the dimensions measured using actual lesions. RESULTS: The average percent error of lesion length, width, and depth based on the 3D images ranged from approximately 8% to 12% when using the thinnest magnetic resonance slice thickness (0.7 mm). CONCLUSIONS: Three-dimensional reconstructed images derived from thin-slice magnetic resonance imaging can provide reasonable representations of true articular cartilage lesion dimensions.

Animals↗

Serum therapy for Cryptococcal meningitis.

Three patients were treated with combined amphotericin B and rabbit anticryptococcal antibody in the 1960s. Rabbit antibody was administered intravenously and was well tolerated. For each patient, administration of rabbit antibody resulted in the appearance of serum Cryptococcus neoformans agglutinins. For two patients the administration of rabbit antibody resulted in negative serum latex tests for cryptococcal antigen. This limited experience with adjunctive antibody therapy provides valuable precedents if antibody therapy is used again for treatment of human cryptococcosis.

Aged↗

Fluconazole and amphotericin B antifungal therapies do not negate the protective effect of endogenous tumor necrosis factor in a murine model of fatal disseminated candidiasis.

In systemic candidiasis, endogenously produced tumor necrosis factor (TNF)-alpha prolongs survival of the infected host. To determine whether endogenously produced TNF-alpha has a beneficial effect beyond that provided by antifungal therapy, survival was assessed in infected mice that received fluconazole or amphotericin B alone and in combination with anti-TNF-alpha antibody. Neutralization of serum TNF-alpha did not affect survival in fluconazole recipients; however, for amphotericin B recipients, it significantly shortened mean survival. For both fluconazole and amphotericin B recipients, colony counts in organs were significantly higher in animals that also received anti-TNF-alpha antibody. Administration of anti-TNF-alpha antibody with amphotericin B or fluconazole did not affect the morphology of fungi or the inflammatory response in kidneys. This study suggests that exogenous TNF-alpha and drugs that increase the endogenous production of TNF-alpha by the host may be useful adjuncts to fluconazole and amphotericin B for the treatment of systemic candidiasis.

Amphotericin B↗

Lightning injury of the tympanic membrane.

Lightning injury to the ear is known, but specific reports are lacking. Four patients with tympanic membrane perforations who were managed surgically are reported. Their presentations, evaluations, intraoperative findings, and outcomes are discussed as they relate to the proposed pathogenic mechanisms. The authors' standard wide exposure tympanoplasty approach with two layer tympanic membrane repair is described. The added steps in performing this procedure may be necessary to ensure a good result in this unique group of patients.

Adolescent↗

Primary cutaneous infection by Aspergillus ustus in a 62-year-old liver transplant recipient.

We report the first case of primary cutaneous aspergillosis caused by Aspergillus ustus, a species that seldom infects human beings. The patient, a 62-year-old liver transplant recipient with end-stage hepatitis C-induced cirrhosis, was receiving the experimental immunosuppressive drug FK-506. Trauma to the skin of the right arm from tape and from an arm board holding intravenous and intraarterial catheters in place and to the left leg from an occlusive knee brace may have contributed to this unusual mycosis. The patient's cutaneous aspergillosis responded to a combination of intravenous amphotericin B and topical terbinafine cream. Although the patient died shortly thereafter from hepatic failure, there was no evidence of systemic aspergillosis.

Aspergillosis↗

Comparative capacity of four antifungal agents to stimulate murine macrophages to produce tumour necrosis factor alpha: an effect that is attenuated by pentoxifylline, liposomal vesicles, and dexamethasone.

The efficacy and toxicity of certain antifungal agents may be related to their ability to induce the production of cytokines by mononuclear phagocytes. The capacity of incremental concentrations of fluconazole, 5-fluorocytosine (5-FC), amphotericin B (AmB), and liposomal AmB (LAB) to stimulate murine peritoneal and RAW 264.7 macrophages to secrete tumour necrosis factor alpha (TNF alpha) after 3, 6 and 24 h incubation was assessed by L929 cytotoxic bioassay. Fluconazole (2.5-40 mg/L) and 5-FC (25-100 mg/L) did not have a stimulatory effect. However, AmB (0.25-10 mg/L) elicited TNF alpha production by macrophages. This response was concentration-dependent, and peak TNF alpha levels were detected between 3 and 6 h. This effect was attenuated by incorporation of AmB into liposomal vesicles and by pretreating macrophages with pentoxifylline or dexamethasone. AmB I mg/L in combination with 1 x 10(6) cfu of Candida albicans stimulated peritoneal macrophages to produce similar quantities of TNF alpha as AmB alone, and two- to four-fold more TNF alpha than C. albicans alone. Thus, this study suggests that: (1) the immunomodulatory activity and toxicities of AmB, in part, may be attributed to the capacity of this drug to stimulate macrophages to secrete TNF alpha, (2) the TNF alpha that is produced by macrophages in response to AmB may have clinical relevance even in the face of C. albicans infection, and (3) the failure of fluconazole, 5-FC, and LAB to elicit a TNF alpha response may explain their improved side-effect profiles.

Amphotericin B↗

Tumor necrosis factor alpha has a protective role in a murine model of systemic candidiasis.

The role of tumor necrosis factor alpha (TNF-alpha) in host defense against systemic Candida albicans infection was evaluated in a murine model of systemic candidiasis in which uniform death occurred between 5 and 6 days after infection. TNF-alpha was first detected at 16 h postinfection and progressively increased thereafter. Peak levels (700 to 900 pg/ml) were measured in mice near death. Administration of 0.5 to 1.0 mg of polyclonal immunoglobulin G (IgG) TNF-alpha antibody (TNF-alpha Ab) to mice 2 h preinfection neutralized serum TNF-alpha for up to 30 h. However, this regimen shortened survival from a mean of 5.5 days for IgG controls to 3.4 days (P = 1.9 x 10(-12)). Semiquantitative cultures of spleen, lung, liver, and kidney conducted at 1, 2, and 3 days postinfection found colony counts of spleen and kidney to be significantly higher for TNF-alpha Ab recipients but only for the first 48 h. Administration of 1.5 and 1.0 mg of TNF-alpha Ab at 2 h before and 48 h after fungal injection, respectively, shortened the mean survival from 4.9 to 2.3 days (P = 5.2 x 10(-8)). This regimen neutralized serum TNF-alpha throughout infection. With this regimen, colony counts of all organs were significantly higher in TNF-alpha Ab recipients at 1, 2, and 3 days postinfection. Histopathologic studies showed an increase in the number and size of C. albicans foci in tissues. Peripheral leukocyte counts and inflammatory response in tissue were similar for TNF-alpha Ab and IgG sham recipients. In vitro, incubation of C. albicans with four to eight times the peak serum levels of TNF-alpha for up to 24 h did not inhibit the rate of germ tube or pseudohypha formation. Thus, TNF-alpha that was produced during infection with C. albicans augmented host resistance against this organism and prolonged survival. The protective effect of TNF-alpha was not mediated by increased leukocytes in blood or tissues nor by a direct anticandidal effect of TNF-alpha. This study suggests that the administration of exogenous TNF-alpha may enhance host resistance against systemic C. albicans infection and may improve host survival.

Animals↗

Endoscopy in otology and neurotology.

Since the early 1980s rigid endoscopes have been used by otorhinolaryngologists in the United States primarily for sinus surgery. Recently rigid endoscopes have been used as an adjunct to standard otologic and neurotologic procedures. Diagnostic inspection of the middle ear can be performed through a myringotomy incision to rule out perilymphatic fistula, for identification of cholesteatoma, or for evaluation of the status of the ossicular chain. During chronic ear surgery endoscopes can be used to locate hidden cholesteatoma in difficult to visualize areas such as the eustachian tube, attic, sinus tympani, and beneath an intact posterior canal wall. In acoustic neuroma surgery in which hearing preservation is an objective endoscopes are used to inspect the lateral aspect of the internal auditory canal (IAC) for residual tumor. During vestibular neurectomy endoscopes are used to view the IAC and to help identify the cochleovestibular cleavage plane. The applications, techniques, and limitations of rigid endoscopy in otology and neurotology are discussed.

Cholesteatoma↗

Evidence of abnormal stromelysin mRNA expression in suspected carriers of otosclerosis. A possible molecular marker.

OBJECTIVE: There is strong evidence that otosclerosis is a genetic disease affecting bone remodeling. We propose that, if otosclerosis is genetic, it will manifest itself universally, particularly at the mRNA transcription level. DESIGN: Skin biopsy specimens were taken in a single blind from human subjects who had been clinically and surgically identified as having otosclerosis. SETTING: Subjects were volunteers from the community, identified through hospital records. All procedures were carried out in a clinical research facility. PATIENTS: Twenty-one volunteers underwent a biopsy, including those positively identified as having otosclerosis (n = 4), their blood relatives (n = 8), or nonrelatives with normal hearing and no known history of otosclerosis (n = 9). INTERVENTION: Three connective tissue remodeling factors, procollagenase, prostromelysin, and tissue inhibitor of metalloprotease, were analyzed. The mRNA was extracted from each biopsy specimen, hybridized against radiolabeled cDNA, and quantitatively measured by radioautography. MAIN OUTCOME MEASURE: We expected to see significant differences in the pattern of mRNA expression for one or more of the three measured bone remodeling factors in otosclerotics, compared with age- and sex-matched negative controls. RESULTS: Two of the otosclerotic subjects had abnormally low levels of mRNA for prostromelysin and two had higher than normal levels. In three (75%) of the four, variability of mRNA expression among procollagenase, prostromelysin, and metalloprotease tissue inhibitor was higher than normal. Three (38%) of the eight relatives showed a similar pattern and two (22%) of the nine control subjects also tested as abnormal. CONCLUSION: This observed variability in otosclerotic subjects might be a manifestation of a genetic control defect, and abnormal stromelysin mRNA expression could serve as a genetic marker for otosclerosis.

Adolescent↗

Thermal biofeedback as an effective substitute for sympatholytic medication in moderate hypertension: a failure to replicate.

Thirty-three moderate hypertensives were converted to a 2-drug regimen of metoprolol and diuretic and BPs stabilized at a well-controlled level. They then completed one of three conditions over an 8-week interval: (I) 16 sessions of TBF (hand and foot warming); (II) 16 sessions of frontal EMG-BF; (III) regular home monitoring of BP. Attempts were then made to withdraw the patients from the sympatholytic medication. Those successfully withdrawn were followed up for one year. There were no significant advantages for TBF over the other two conditions in the short term or with long-term follow-up. Only 27% of treated patients (including Condition III failures who were remedicated and treated with TBF) were successfully off of the sympatholytic at a one-year follow-up. The generally poor results on clinical outcome were confirmed by clinic BPs, home BPs by patients, and 24-hour ambulatory BPs.

Biofeedback, Psychology↗