Biomedical subjects
Publications and source records attributed to D Smith.
The segmental localization of liver tumors is critical to planning appropriate resection. Couinaud's nomenclature is a surgically relevant system of hepatic segmental anatomy, which defines the liver segments by their relationships to vascular structures, hepatic ligaments, and the gallbladder. We demonstrate a way to accurately localize hepatic masses with sonography.
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Restorative proctocolectomy with ileo-pouch-anal anastomosis has become the elective surgical procedure of choice for most of our patients with ulcerative colitis and for selected patients with familial adenomatous polyposis. This report reviews the results of the outcome of patients who have undergone a more radical reconstructive approach for salvage of the pelvic pouch where multiple local procedures have failed. A group of 24 patients were reviewed (19 females, 5 males). The indication for surgery was ulcerative colitis in 22 patients; 10 of the 24 patients were referred from other centers. The 24 patients underwent a mean of 2.9 local salvage procedures per patient. Of the 19 females within the group, 12 had an anastomotic vaginal fistula. The 24 patients were divided into two groups. The first group consisted of 14 patients whose initial pouch was used once again for revisionary surgery. Group 2 comprised 10 patients whose initial pouch was removed and a redo pouch was constructed. Of the 24 patients, only 2 have had their pouches removed. More than 75% of the patients have had a successful outcome using a reconstructive approach. Four patients still have an ileostomy; of these four, two are awaiting closure of their loop ileostomy. Of 18 patients who were evaluable, 13 were considered to have normal daytime continence, and 17 of 18 were sexually functional. Of the 18 evaluable patients, 15 were satisfied with the outcome. Radical reconstructive surgery can be performed where local procedures to effect pouch salvage have failed, and it should be considered as a first-line management where factors dictate that local procedures might fail. The commitment of the surgeon and the patient to achieving a successful outcome is essential. Severe pouch-specific complications can be managed successfully by surgeons who have a specific interest in pelvic pouch surgery and have considerable experience dealing with complications that arise.
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Early identification of enteric injuries following blunt trauma relies on clinical examination, diagnostic peritoneal lavage (DPL), and/or computed tomography (CT) scan. Limitations in each approach may result in diagnostic delays and potentially increased complications. The purpose of this study was to evaluate the ability of early DPL and CT scans in identifying enteric injuries requiring surgical repair and to determine the impact of injury time to definitive repair on complication rates. A retrospective review of patients admitted to the Butterworth Hospital Level I Trauma Center between January 1, 1990 and December 31, 1996 identified 69 appropriate patients. Three study groups were treated as follows: laparotomy on clinical examination (N = 7), laparotomy after initial DPL (N = 28), and laparotomy after initial CT (N = 34). Early DPL missed 5 (18%) enteric injuries, which was significantly fewer than the 13 (38%) missed by CT scan. Review of these 13 CT scans revealed 6 examinations not suggesting enteric injury and 7 with signs suggestive of injury. Four injuries missed by CT subsequently were found by delayed DPL. Morbidity rates in either group increased when injury time to definitive repair was >24 hours (18-50%). The results indicate that early DPL and CT have limitations in blunt enteric injuries. However, morbidity and mortality rates did not increase until repair was delayed >24 hours postinjury. Also, delayed DPL successfully identified these injuries in four patients after negative CT. Therefore, in patients at high risk for enteric injuries, there may be a role for delayed or repeat DPL after an initially negative DPL or CT.
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Neutrophils play an important part in the development of acute inflammatory injury. Human neutrophils contain high levels of the serine protease elastase, which is stored in azurophilic granules and is secreted in response to inflammatory stimuli. Elastase is capable of degrading many components of extracellular matrix [1-4] and has cytotoxic effects on endothelial cells [5-7] and airway epithelial cells. Three types of endogenous protease inhibitors control the activity of neutrophil elastase, including alpha-1 protease inhibitor (alpha-1PI), alpha-2 macroglobulin and secreted leukoproteinase inhibitor (SLPI) [8-10]. A disturbed balance between neutrophil elastase and these inhibitors has been found in various acute clinical conditions (such as adult respiratory syndrome and ischemia-reperfusion injury) and in chronic diseases. We investigated the effect of NX21909, a selected oligonucleotide (aptamer) inhibitor of elastase, in an animal model of acute lung inflammatory disease [11-14]. This inhibitor was previously selected from a hybrid library of randomized DNA and a small-molecule irreversible inhibitor of elastase (a valine diphenyl ester phosphonate, Fig. 1), by the blended SELEX process [15]. We show that NX21909 inhibits lung injury and neutrophil influx in a dose-dependent manner, the first demonstration of efficacy by an aptamer in an animal disease model.
BACKGROUND: Previous studies have suggested that low plasma cholesterol levels or cholesterol lowering may increase the risk of suicide and violent death. Increased aggression, risk-taking behavior, or depression has been associated with low cholesterol levels in some studies. METHODS: A total of 4240 subjects of the Coronary Artery Risk Development in Young Adults study, aged 23 to 35 years, were included in the study. Analyses were stratified by race (black or white) and sex. Persons in the lowest 10% of plasma total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels were compared with the other participants in each race/sex group, using standardized measures of hostility, anger suppression, depressive symptoms, and anxiety. The relations between 5-year change in hostility and 5-year change in lipid levels also were examined. The relations between lipid levels and high-risk behavior (e.g., violent arguments or having a gun at home) were examined in a subset of subjects. All analyses were adjusted for relevant covariates. RESULTS: In cross-sectional analyses, low total cholesterol levels were not related to any of the psychological measures in any race/sex group. Among black women only, low low-density lipoprotein cholesterol was related to greater anxiety, and low triglycerides were related to lower anger suppression (P < or = .002). Among white men only, increases in hostility during the 5-year follow-up were related to increases in triglycerides (P < .01), but changes in hostility were unrelated to changes in cholesterol levels. Among a subset of 371 subjects with initially elevated total cholesterol (> or = 5.17 mmol/L [> or = 200 mg/dL]) and a non-medicated decrease of 0.52 mmol/L (> or = 20 mg/dL) or more during 5 years, hostility decreased in a univariate analysis (P < .001). High-risk behaviors also were not associated with low lipid levels. CONCLUSION: The results do not support a consistent relation between hostility, negative affect, or high-risk behaviors with low lipid levels or lipid-lowering among young adults.
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Toward a goal of dideoxy sequencing DNA utilizing electrophore labels, we prepared four electrophore-labeled DNA oligonucleotide primers. Each primer has a different electrophore and DNA sequence but a common glycol keto (alpha,beta-dihydroxyketo) release group. Cleavage of this latter group by either periodate oxidation or a thermal retroaldol reaction releases the electrophores for detection by mass spectrometry. Successful sequencing data with these primers was obtained by capillary electrophoresis on an ABI Model 310 after fluorescence dideoxy terminator cycle sequencing reactions were conducted. In a separate experiment, it was demonstrated that a cocktail of the four electrophore DNA primers could be detected as a dried sample spot by CO2 laser desorption/capillary collection/gas chromatography electron capture mass spectrometry. These results establish some feasibility for our long-term goal of high-speed multiplex electrophore mass tag dideoxy DNA sequencing. Ultimately we plan to use a higher number of electrophore mass tags and to rely on direct detection of the desorbed electrophores by electron capture time-of-flight mass spectrometry.
Custom designed analogs of the natural anti-bacterial peptide cecropin B (CB) have been synthesized; cecropin B-1 (CB-1) was constructed by replacing the C-terminal segment (residues 26 to 35) with the N-terminal sequence of CB (positions 1 to 10 which include five lysine residues). The second analog, CB-2, is identical to CB-1 except for the insertion of a Gly-Pro residue pair between Pro-24 and Ala-25. These peptides were used to investigate their anti-liposome, anti-bacterial and anti-cancer activities. The strength of anti-liposome activity is reduced two- to three-fold when the analogs are used instead of natural CB based on DL50 analysis. Similarly, the potency of these analogs on certain bacteria is about two- to four-fold lower than those of CB based on LC measurements. In contrast, on leukemia cancer cells, the potency of CB-1 and CB-2 is about two- to three-fold greater than that of natural CB based on IC50 measurements. All CB, CB-1 and CB-2 peptides have comparable helix contents according to CD measurements. These results indicate that the designed cationic lytic peptides, having extra cationic residues, are less effective in breaking liposomes and killing bacteria but more effective in lysing cancer cells. The possible interpretations for these observations are discussed.
Apoptosis is postulated to be involved as an anti-viral immune mechanism by killing infected cells before viral replication has occurred. The Fas-Fas ligand interaction is a powerful regulator of T cell apoptosis and could potentially act as a potent anti-viral immune mechanism against T cell tropic virus such as human immunodeficiency virus (HIV). We investigated the status of Fas ligand in peripheral blood mononuclear cells (PBMCs) obtained from persons infected with HIV. We found that monocytes in freshly isolated PBMCs from healthy individuals possess cell surface Fas ligand. In contrast, monocytes in freshly isolated PBMCs from HIV-infected patients had no detectable Fas ligand on the cell surface. Consistent with these findings of surface expression, Fas ligand activity was deficient in the cells from HIV-infected persons. The effect of replacing Fas ligand activity on HIV production by patients' cells was assessed in an in vitro assay. The addition of a functional anti-Fas antibody to PBMCs from HIV-infected individuals inhibited viral production by greater than 90% without affecting lymphocytic function. These findings suggest the possibility of a new therapeutic modality for the treatment of HIV-infected individuals based on the reconstitution of Fas ligand activity.
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