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Biomedical subjects

L E Smith

Publications and source records attributed to L E Smith.

At least 55 records · Page 3Linked to original sources
PubMed1995

Intraoperative reasons for abandoning ileal pouch-anal anastomosis procedures.

PURPOSE: Ileal pouch-anal anastomosis (IPAA) has become the operation of choice for most patients with chronic ulcerative colitis and familial adenomatous polyposis. However, because of technical or disease factors at the time of pouch construction, IPAA must sometimes be abandoned. A retrospective review was conducted to find reasons for IPAA failure or abandonment. METHODS: Since 1981, 103 patients have had to have an IPAA procedure at the George Washington University Medical Center in Washington, DC. All charts were reviewed and data retrospectively collected. RESULTS: Six of 103 patients (six percent) were unable to have IPAA constructed. Five patients ultimately received a standard end ileostomy, and one had an ileorectal anastomosis. The reasons for abandoning the IPAA procedure were an ischemic pouch, failure to reach the anus, poorly controlled presacral hemorrhage, desmoid of the mesentery, and finding incurable colon carcinoma. CONCLUSIONS: Information regarding the risk of failure or abandonment during the IPAA procedure should be discussed with the patient during preoperative counseling and must be included as an element of informed consent.

Adenomatous Polyposis Coli↗
PubMed1994

Microbiology of human immunodeficiency virus anorectal disease.

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19-59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent), Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas. Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months +/- 2.9 SEM (range, 1-94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.

Acyclovir↗
PubMed1994

Oxygen-induced retinopathy in the mouse.

PURPOSE: To develop oxygen-induced retinopathy in the mouse with reproducible and quantifiable proliferative retinal neovascularization suitable for examining pathogenesis and therapeutic intervention for retinal neovascularization in retinopathy of prematurity (ROP) and other vasculopathologies. METHODS: One-week-old C57BL/6J mice were exposed to 75% oxygen for 5 days and then to room air. A novel fluorescein-dextran perfusion method has been developed to assess the vascular pattern. The proliferative neovascular response was quantified by counting the nuclei of new vessels extending from the retina into the vitreous in 6 microns sagittal cross-sections. Cross-sections were also stained for glial fibrillary acidic protein (GFAP). RESULTS: Fluorescein-dextran angiography delineated the entire vascular pattern, including neovascular tufts in flat-mounted retinas. Hyperoxia-induced neovascularization occurred at the junction between the vascularized and avascular retina in the mid-periphery. Retinal neovascularization occurred in all the pups between postnatal day 17 and postnatal day 21. There was a mean of 89 neovascular nuclei per cross-section of 9 eyes in hyperoxia compared to less than 1 nucleus per cross-section of 8 eyes in the normoxia control (P < 0.0001). Proliferative vessels were not associated with GFAP-positive astrocyte processes. CONCLUSIONS: The authors have described a reproducible and quantifiable mouse model of oxygen-induced retinal neovascularization that should prove useful for the study of pathogenesis of retinal neovascularization as well as for the study of medical intervention for ROP and other retinal angiopathies.

Animals↗
PubMed1994

Effect of light on oxygen-induced retinopathy in the mouse.

PURPOSE: To examine the effect lf light on retinal neovascularization and vasculogenesis in a reproducible and quantifiable model of oxygen-induced proliferative retinopathy in the mouse. METHODS: C57Bl/6J mice were reared in room air, 68% oxygen, or 75% oxygen and were exposed to darkness, low cyclical light (200-350 lux), or high-intensity continuous light (3000-4500 lux). The entire retinal vascular pattern was visualized in fluorescein-dextran perfused flat-mount preparations. Proliferative retinopathy was quantified by counting neovascular nuclei in 6 microns cross-sections of whole eyes. RESULTS: Light exposure did not exacerbate the proliferative retinopathy that was seen after 68% oxygen exposure, which induced a meager proliferative response, nor after 75% oxygen exposure, which induced an exuberant proliferative response. In room air, retinas from all three illumination groups had normal vascular patterns. CONCLUSIONS: In this model of oxygen-induced retinopathy, under the conditions tested, light neither exacerbated the hyperoxia-induced neovascularization nor affected normal retinal vascular development.

Animals↗
PubMed1993

Microscopic visualization of the retina by angiography with high-molecular-weight fluorescein-labeled dextrans in the mouse.

Methods currently available for the examination of the retinal vasculature of laboratory animals have significant drawbacks. Fluorescein angiography of rodent eyes is hampered by a poor view of the peripheral retina and difficulty in performing fundus photography. Methods of staining or filling retinal vessels are unreliable, labor-intensive, or have high backgrounds. We have developed a novel technique that is quick, simple, and accurate. Fluorescein-labeled 2 million molecular weight dextrans are used to fill the retinal vasculature of mice in vivo, followed by removal of the retina, fixation in paraformaldehyde, and examination of the vascular pattern in whole mount preparations by fluorescence microscopy. We found that fluorescein and fluorescein-labeled low-molecular-weight dextrans (40,000-500,000) are not suitable as they leak out of the vasculature to stain the entire retina in whole mount preparations. By contrast, fluorescein-labeled 2 million molecular weight dextrans remain in the vasculature for many months without diffusion or decay. Under low magnification, the entire retinal vasculature can be visualized at one time. By focusing from one plane to another, the superficial, connecting, or deep vascular layers are delineated. The background fluorescence is very low. We have successfully used this technique in over 20 mice per day to document retinal angiogenesis in a model of oxygen-induced proliferative retinopathy.

Animals↗
PubMed1993

Genetic instability on chromosome 16 in a human B lymphoblastoid cell line.

Mutagenesis at the aprt locus in TK6 human lymphoblasts has been found to occur at an unusually high rate (1.2 x 10(-9)) for a homozygous diploid locus. Evaluation of linked microsatellite polymorphisms demonstrated that loss of heterozygosity (LOH) accompanies conventional intragenic sequence alterations in each APRT- mutant. LOH occurred without allele preference. The extent of loss was highly uniform, ranging from 16q12 to 16qter in 36/38 APRT- mutants. Fluorescence in situ hybridization (FISH), used in conjunction with microsatellite analysis, demonstrated that the loss was not attributable to physical deletion, nondisjunction, or nondisjunction with reduplication of the remaining chromosome. LOH thus appears to be recombinationally mediated. FISH analysis also detected translocations affecting chromosome 16 in 4/20 APRT- mutants examined. APRT- mutants appear to arise as part of a genetic instability phenomenon since three distinct genetic alterations affecting chromosome 16 are recovered in single clones at a detectable rate. These events may be mechanistically related to early events in gene amplification.

Adenine Phosphoribosyltransferase↗
PubMed1993

Evidence for high-frequency allele loss at the aprt locus in TK6 human lymphoblasts.

The aprt locus in TK6 human lymphoblasts has been previously shown to have an unusual mutation frequency (5 x 10(-8) and a gene dosage of 2. Measurements of mutation rate (1.2 x 10(-9)) reported here, confirm the mutation-frequency observations. These results are not easily accommodated by models of the gene as functionally homozygous or heterozygous. Characterization of all exon and intron sequences identified no polymorphism which could distinguish two heterozygous aprt alleles. Furthermore, autoradiographs of 16 spontaneous APRT- mutants demonstrate a variety of unique sequences. If aprt were heterozygous, wild-type sequence from the alternate allele would be observed at positions where mutations have occurred. These observations cannot be explained by conventional loss of heterozygosity in which the same mutated allele would be repeatedly recovered. We therefore propose that aprt is a functionally homozygous locus. APRT- mutants may arise by conventional mutation of one allele, and high-frequency loss or conversion of the alternate allele.

Adenine Phosphoribosyltransferase↗
PubMed1992

Perineal manifestations of HIV infection.

Individuals who are seropositive for the human immunodeficiency virus (HIV) frequently have disorders affecting the anorectum, yet little has been reported on this subject. We reviewed our initial experience with patients with HIV referred to the Division of Colon and Rectal Surgery. Forty patients (age range, 19-45 years; mean, 32.2 years) were seen between 1985 and 1989. The mean duration of symptoms was six months (range, one week to six years). In 25 patients (63 percent), more than one anorectal condition was identified. Condylomata were seen in 21 patients (52 percent), and in 11 these were associated with other pathologies. Fistulas and/or abscesses were identified in 15 patients (37 percent). Three had a "watering-can perineum," all without any identifiable predisposing factors. Nineteen patients had symptomatic hemorrhoids (seven), fissures (17), and/or perianal herpes infections (five), usually in combination with other lesions (89 percent). Three individuals developed neoplastic processes. Rectal disease was discovered in addition in nine patients. This included nonspecific proctitis in four, a rectal mass in four (polyps, two; rectal diverticulum, one; and Kaposi's sarcoma, one), and a nonspecific rectal ulcer in one. Four patients had other symptoms, including diarrhea, incontinence, soiling, frequency, and/or urgency, always in combination with other anal disorders. Seventy-one operative procedures were performed in 31 patients (78 percent). Only six (8 percent) of these were for diagnosis and biopsy alone. Mean follow-up was 15.5 months in the 23 patients followed for greater than one month. Only 6 of 23 (26 percent) had resolution of their problem. Nine (39 percent) developed new perianal conditions. Anorectal disorders are often seen in patients infected with HIV. They may be aggressive, cause significant morbidity, and be difficult to resolve.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Hemorrhoidectomy with lasers and other contemporary modalities.

Hemorrhoids should be classified so that the treatment can be individualized. Minor or asymptomatic hemorrhoids usually do not require any treatment. Diet modification is a useful adjunct in all degrees of hemorrhoids. Fixation procedures may be employed in the office for first-, second-, and minor third-degree hemorrhoids. These techniques are valuable in elderly and poor-risk patients. Excisions may be performed by standard instruments or lasers with good results. These techniques may be employed with local anesthesia and in an outpatient setting. Lasers may be effective as either a fixation device or an excisional tool. The problem is cost and maintenance of the equipment and the cost of the disposable apparatus. If the equipment is already available or can be shared for multidisciplinary use, hemorrhoidectomy can be accomplished in a cost-effective manner with excellent results.

Female↗
PubMed1992

Alterations in endothelial superoxide dismutase levels as a function of growth state in vitro.

Damage to the retinal vasculature in retinopathy of prematurity is primarily at the level of the growing neovascular front. This clinical observation in combination with experimental observations that correlate the induction of superoxide dismutase (SOD) activity with differentiation led to the hypothesis that the basis for the relative vulnerability to oxygen lies in the relative "undifferentiated" nature of proliferating endothelial cells (EC). To test this hypothesis, an in vitro model of microvascular EC was used and levels of SOD activity were assayed as a function of growth state and differentiation. The SOD activity was elevated significantly in EC that stopped growing as a contact-inhibited monolayer compared with its activity in cells in their log phase of growth. In addition, SOD levels were elevated in microvascular cells that stopped growing and were organized into a network of capillary-like tubes, the ultimate differentiated state of microvascular EC. To understand the mechanism of increases in SOD activity with differentiation, the effect of extracellular matrix synthesized by a confluent monolayer of EC was examined as was artificial growth arrest caused by mitomycin. Both treatments led to an increase in SOD activity over control cells. Thus, it is possible that SOD activity in cells is modulated by information provided from the extracellular matrix and "intracellular" signals that indicate cessation of cell growth. These data support the hypothesis that the growing front of retinal microvessels is more vulnerable to effects of oxygen-induced damage because of their relatively undifferentiated state with respect to the oxygen radical-scavenging enzyme system of SOD.

Adrenal Cortex↗
PubMed1991

The interaction between CD8+ cytotoxic T cells and Leishmania-infected macrophages.

Leishmania is resident within the macrophages of its vertebrate host. In any intramacrophage infection, where the pathogen is present in a form capable of mediating cell to cell transmission, the contribution of a cytotoxic T cell response to protective immunity is questionable. This study presents data from an in vitro model designed to elucidate the outcome of an interaction between CD8+, cytotoxic T cells and infected macrophages. Experiments were conducted with an H-2d-restricted, cytotoxic CD8+ T cell clone and Leishmania parasites present in mixed macrophage cultures, with the parasites confined to either histocompatible BALB/c macrophages, or incompatible CBA macrophages. Initial experiments indicated that the viability of Leishmania was unaffected by the lysis of its host macrophage by cytotoxic T cells. However, extended experiments showed that the parasites were killed between 24 and 72 h. The same results were obtained regardless of whether the parasites were resident in the target, BALB/c, macrophages or the bystander, CBA, macrophages. Addition of neutralizing, anti-IFN-g antibody to the cultures ablated most of the leishmanicidal behavior, indicating that parasite death was attributable to macrophage activation, resulting from cytokine secretion from the T cells following the initial recognition event.

Animals↗
PubMed1991

Endoscopic sinus surgery: outcome in 155 cases.

For this retrospective study of endoscopic sinus surgery, charts of 22 patients from a medical center and 133 patients from a private practice (N = 155) were reviewed. Preoperative complaints, clinical findings, computed tomographic evidence of extent of sinus disease, surgical outcome, possible predictors of success, and complications were considered. Indications for endoscopic surgery were persistence of symptoms despite aggressive medical therapy and radiologic evidence of a significant sinus abnormality. Median followup was 12 months. Hemorrhage occurred postoperatively in two patients (1.5%); 17 patients required additional endoscopic surgery. Overall, 140 (91%) patients believed that the surgery was beneficial. Patients with facial pain preoperatively showed the greatest improvement. All patients having simultaneous septoplasty (N = 64) had successful outcome. The total number of opacified sinuses was not a predictor of outcome, but opacificaiton of the sphenoid sinus correlated with a poorer outcome. The patients seen at the medical center had poorer results, but had a larger number of opacified sinuses, were more likely to have had previous sinus surgery, and were more likely to have underlying medical conditions contributing to their sinus disease.

Academic Medical Centers↗
PubMed1991

Adenocarcinoma of the colon and rectum in patients less than 40 years of age.

From 1962 to 1988, 50 of 801 patients with adenocarcinoma of the colon and rectum treated at the National Naval Medical Center were less than 40 years old. Symptoms were present in 47 of the younger patients at presentation. The mean duration of time from the onset of symptoms to diagnosis in this group was 4.9 months. Risk factors for carcinoma of the colon and rectum were identified in 14 of 50 patients less than 40 years old. A significantly greater proportion of patients less than 40 years old had Stage C disease compared with the older group of patients (42 versus 22 per cent, p = 0.014). Stage B disease was more common in patients more than 40 years of age (44.8 versus 26.0 per cent, p = 0.014). The proportion of patients with Stages A and D disease was similar in both age groups. The cumulative survival rate in this group at five and ten years was 43 and 34 per cent, respectively. The five year survival rate in patients less than 40 years old with Stage B disease was 76 per cent and with Stage C disease, 37 per cent. All young patients with Stage D disease were dead at 28 months. Synchronous and metachronous carcinomas of the colon and rectum were uncommon in patients less than 40 years old. Patients less than 40 years of age with carcinoma of the colon and rectum are usually symptomatic and have advanced disease at the time of presentation. Survival time for these patients for each stage of disease is similar to the over-all population of patients with carcinoma of the colon and rectum.

Adenocarcinoma↗
PubMed1990

A review of the depressive personality.

A depressive type of personality disorder has been described by both German phenomenologists and psychoanalysts and has been used by clinicians for years. Although this personality type has been included in standard international nosologic systems (ICD-9), it has never been recognized in DSM. This literature review identifies and explores the issues relevant to the possible inclusion of such a category--an axis II personality disorder linked to axis I depressive disorder--in the upcoming DSM-IV.

Depression↗