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Biomedical subjects

S E Wilson

Publications and source records attributed to S E Wilson.

At least 163 records · Page 9Linked to original sources

Clinical correlates of anaerobic bacteriology in peritonitis.

Recent surgical reports indicate that for patients with secondary bacterial peritonitis, surgeons do not routinely use the identification of the bacterial pathogens and determination of their antimicrobial susceptibilities in choosing antimicrobial therapy. Further, some surgeons advocate abandoning the routine practice of obtaining culture specimens from patients with complicated appendicitis, because the data from the clinical laboratory have not been found to have an impact on postoperative care. We review the rationale for continued surveillance of and implementation of bacteriological data in treatment of secondary peritonitis. We also describe in detail the anaerobic flora of secondary peritonitis, the unique susceptibility patterns of these organisms, and the specific virulence factors of anaerobes, particularly Bacteroides fragilis. The fact that clinical investigations sometimes result in treatment failure when gram-negative anaerobes are resistant to the antimicrobials used or when complete antimicrobial susceptibility data are not available emphasizes the need for accurate and early knowledge of the bacteriologic characteristic of the flora of the operative site. We emphasize the relationship of in vitro susceptibility of intraoperative isolates with clinical outcome. We propose a cooperative trial that would demonstrate that successful antimicrobial therapy should be based on the susceptibility of the flora of the operative site, which correlates with clinical outcome.

Animals↗

Meropenem versus tobramycin plus clindamycin for treatment of intraabdominal infections: results of a prospective, randomized, double-blind clinical trial.

The efficacy of meropenem was compared to that of the combination of tobramycin plus clindamycin (T/C) in a multiinstitutional clinical trial of treatment for patients suffering intraabdominal infection. Among the 177 patients enrolled and randomized, 127 were clinically evaluable and 86 were microbiologically evaluable. Analysis of data on an intent-to-treat basis for all randomized patients and on the basis of a successful outcome (absence of any infection) for clinically evaluable patients failed to detect any difference in efficacy between the two treatments. Infection was cleared in 92% of meropenem- and 89% of T/C-treated clinically evaluable patients. Eradication of pathogens also was similar in the two treatment groups. Overall, adverse drug experiences were comparable between the two treatment groups, with the exception of an increase in serum creatinine level (which occurred more frequently in patients receiving T/C). Meropenem appears to be efficacious for the treatment of intraabdominal infections.

Abdomen↗

Meropenem versus imipenem/cilastatin in the treatment of hospitalized patients with skin and soft tissue infections.

Meropenem is a new carbapenem antibiotic shown to resist degradation by renal dehydropeptidase I. In a multicenter, open-label, prospective trial, we compared the efficacy and safety of meropenem with imipenem/cilastatin in patients with skin and soft tissue infections. Patients received either 500 mg of meropenem every 8 hours (n = 184) or 500 mg of imipenem/cilastatin every 6 hours (n = 193), by intravenous infusion for an average of 6 to 7 days. Satisfactory clinical responses were achieved in 120 (98%) of 123 assessable meropenem-treated patients and in 120 (95%) of 126 assessable imipenem/cilastatin-treated patients. Satisfactory bacteriologic responses were achieved in 120 (98%) of 123 assessable meropenem-treated patients and in 120 (95%) of 126 assessable imipenem/cilastatin-treated patients. Satisfactory bacteriologic response rates were high as well: 94% with meropenem and 91% with imipenem/cilastatin. Between-group differences in satisfactory response rates were not significant (95% confidence interval, -2.29 to 6.93 [clinical]; -2.73 to 10.39 [bacteriologic]). Overall pathogen eradication rates (for aerobes and anaerobes) were slightly higher for meropenem. Elevated liver enzymes were the most frequent adverse events in each treatment group. Meropenem was well tolerated and as effective as imipenem/cilastatin in treatment of hospitalized patients with skin and soft tissue infections.

Abscess↗

Inguinal wound fluid collections after vascular surgery: management by early reoperation.

Inguinal wounds complicated by significant fluid collections after vascular grafting procedures were managed by exploration soon after recognition in 14 patients. Within 24 hours, incisions were reexplored, fluid collections were evacuated and cultured, and closed suction drains were placed. The wound was reapproximated, and broad spectrum antibiotics were given intravenously until 24 hours after removal of the drain. Variables evaluated included spontaneous drainage before exploration, positive intraoperative wound cultures, exposure of graft when the wound was opened, and type of graft used. On careful follow-up, from 5 months to 3.5 years, averaging 14 months, only one patient had an infected graft, occurring 6 months after the wound exploration. There were no complications in wound healing from the inguinal explorations. These results suggest that early exploration and reclosure of clinically significant postoperative fluid collections is safe, results in primary healing, and has a low rate of subsequent graft infection.

Aged↗

Control of lytic development in the Streptomyces temperate phage phi C31.

The repressor gene, c, is required for maintenance of lysogeny in the Streptomyces phage phi C31. The c gene expresses three in-frame N-terminally different protein isoforms at least one of which is thought to bind to a 17bp highly conserved inverted repeat (CIR) sequence found at 18 (or more) loci throughout the phi C31 genome. Here we present evidence that one of these loci, CIR6, and its interaction with the products of the repressor gene are critical in the control of the lytic pathway in phi C31. To the right of CIR6, according to the standard map of phi C31, an 'immediate-early' promoter, ap1, was discovered after insertion of a fragment containing CIR6 upstream of a promoterless kanamycin-resistance gene, aphII, to form pCIA2. pCIA2 conferred kanamycin resistance upon Streptomyces coelicolor A3(2) but not upon a phi C31 lysogen of S. coelicolor. Operator-constitutive (Oc) mutants of pCIA2 were isolated and the mutations lay in CIR6, i.e. CIR6:G14T and CIR6:C2A. Primer extension analysis of RNA prepared from an induced, temperature-sensitive lysogen of S. coelicolor localized a mRNA 5' endpoint 21 bp to the right of CIR6. The importance of the ap1/CIR6 region in the regulation of lytic growth was demonstrated by the analysis of a virulent mutant, phi C31 vir1, capable of forming plaques on an S. coelicolor phi C31 lysogen. phi C31vir1 contained a DNA inversion with the breakpoints lying within the integrase gene (which lies approximately 7 kbp to the right of CIR6) and in the essential early region between CIR6 and the -10 sequence for ap1. The separation of ap1 from its operator was thought to be the basis for the virulent phenotype in phi C31 vir1. Band-shift assays and DNase I footprinting experiments using purified 42 kDa repressor isoform confirmed that CIRs 5 and 6 were indeed the targets for binding of this protein. The 42 kDa repressor bound to CIR6 with higher affinity than to CIR5 in spite of their identical core sequences. Repressor bound at CIR6 facilitated binding at CIR5. The high-affinity binding to CIR6 was abolished with the Oc mutant, CIR6:G14T. Hydroxyl radical footprinting and dimethyl sulphate methylation protection of the 42 kDa repressor-CIR6 interaction suggested that the protein bound in the major groove and to one face of the DNA.

Bacteriophages↗

Carbapenems: monotherapy in intra-abdominal sepsis.

Meropenem is the first of a new class of dehydropeptidase-stable carbapenems which is highly active against the microflora associated with intra-abdominal infection. Three randomised, prospective multicentre studies, have compared meropenem monotherapy with imipenem/cilastatin and cefotaxime plus metronidazole in the treatment of intra-abdominal infections: meropenem (1 g) versus cefotaxime (2 g) plus metronidazole (500 mg); meropenem (1 g) versus imipenem/cilastatin (1 g); meropenem (500 mg) versus imipenem/cilastatin (500 mg), all administered intravenously every 8 hours. Of the 641 patients with intra-abdominal infections randomised to treatment, 555 (87%) were clinically evaluable and 445 (69%) were bacteriologically evaluable. At the end of treatment a majority of the patients in each of the 3 studies was clinically cured or improved (91-100%). There were no clinically significant differences between the treatment regimens. Meropenem was effective over a range of intra-abdominal infections and as well tolerated as imipenem/cilastatin, and cefotaxime plus metronidazole.

Adult↗

Operative site bacteriology as an indicator of postoperative infectious complications in elective colorectal surgery.

Toward the completion of elective colorectal operations, 75 patients had qualitative aerobic and anaerobic cultures of specimens obtained from peritoneal irrigation fluid, anastomoses sites, and abdominal wound irrigation fluid to determine if a correlation exists between intraoperative flora and postoperative infectious complications. Patients enrolled in this prospective study received a mechanical bowel prep and a 12-18 hour course of perioperative intravenous antibiotics. Comparisons were made between the 60 (80%) patients who had no postoperative infections and the 15 (20%) who developed postoperative infectious complications (9 wound infections, 6 intraabdominal infections). There were significantly more low anterior resections in patients who developed postoperative infection compared to those who had no postoperative infection (26% vs 2%), while there were more colocolostomies in the group with no infections (38% vs 7%). Streptococcus spp., Bacteroides fragilis group, and Escherichia coli were the most commonly isolated organisms from each of the three sites sampled. Isolation of > or = 3 organisms from incisional wound cultures (P = 0.017) and < or = 4 organisms from peritoneal irrigation (P = 0.009) or anastomotic culture (P = 0.004) correlated with development of postoperative infectious complications. Thus, patients with infectious complications had significantly more isolates than those without infectious complications, and were more likely to have had a low anterior resection. These data suggest that future clinical studies should reexamine the duration of perioperative antimicrobials based on early laboratory reports of qualitative and quantitative operative site bacteriology.

Abdomen↗

Clinical trials of extended spectrum penicillin/beta-lactamase inhibitors in the treatment of intra-abdominal infections. European and North American experience.

The clinical results with the beta-lactam/beta-lactamase inhibitor class of antimicrobials in the treatment of intra-abdominal infections are reviewed. The three agents now in clinical use--ampicillin/sulbactam, ticarcillin/clavulanate, and piperacillin/tazobactam--are effective against a broad variety of gram-positive and gram-negative organisms. The beta-lactamase inhibitor is an irreversible inactivator of beta-lactamase enzymes, which are produced by many gram-negative and gram-positive organisms. Randomized, prospective, clinical trials of each agent indicate clinical cure rates > 85% that are not significantly different from those obtained with second-generation cephalosporin or aminoglycoside plus antianaerobic comparators, with the exception of one study. Piperacillin/tazobactam has also been compared with imipenem, with equivalent or superior outcomes, depending on the dose of the imipenem comparator. Side effects in the non-penicillin-allergic patient are few. The incidence of abnormal renal function tests are generally lower than that obtained with aminoglycoside plus antianaerobic therapy. Introduction of this new beta-lactam antimicrobial group provides another important strategy for the adjunctive management of surgically treated, community-acquired, intra-abdominal infection.

Abdomen↗

Concordance of human leukocyte antigen haplotype-sharing, CD4 decline and AIDS in hemophilic siblings. Multicenter Hemophilia Cohort and Hemophilia Growth and Development Studies.

OBJECTIVE: To assess the association between human leukocyte antigen (HLA) haplotypes and the incidence rates of CD4 decline to < 20% and to AIDS. DESIGN: Retrospective cohort study of 95 HIV-1-infected hemophilic sibling pairs. METHODS: HLA haplotype-sharing between siblings was assigned on the basis of serologic typing of HLA class I alleles and molecular typing of HLA class II alleles. Concordance of time to CD4 decline to < 20% and to AIDS within and between sibling pairs was assessed by analysis of variance models and calculations of intraclass correlation coefficients. The age-adjusted relative risks of these two endpoints for unique class II haplotypes were determined from proportional hazards models. RESULTS: Sibling pairs sharing one or two haplotypes were significantly concordant in CD4 decline and AIDS status within 5 years of seroconversion. No concordance was found in pairs sharing zero haplotypes. At 6-10 years after seroconversion, significant concordance of these two endpoints was also observed in the pairs sharing one haplotype. The concordant results were not explained by the use of zidovudine within the pairs. Among the individuals in this cohort, the relative hazards for CD4 decline to < 20% and for AIDS were significantly elevated for one class II haplotype (DQB1*0501, DQA1*0101, DRB1*0101). In addition, the risk for AIDS was significantly increased for two other class II haplotypes (DQB1*0603, DQA1*0103, DRB1*1300, DRB3*0202 and DQB1*0301, DQA1*0501, DRB1*1400, DRB3*0202) and significantly decreased for one haplotype (DQB1*0302, DQA1*0301, DRB1*0401, DRB4*0101). CONCLUSIONS: These data demonstrate that HIV-1 disease progression is associated with the genes in the major histocompatibility complex that regulate the host's immune response.

Acquired Immunodeficiency Syndrome↗

Expression of E6/E7 or SV40 large T antigen-coding oncogenes in human corneal endothelial cells indicates regulated high-proliferative capacity.

PURPOSE: Human corneal endothelial cells are thought to have limited capacity for proliferation. Little is known about the mechanisms that regulate the proliferation of these cells. The authors introduced oncogenes into human corneal endothelial cells to modulate proliferation. In addition, they sought to establish cell lines to facilitate study of human corneal endothelial cells. METHODS: Early-passage human corneal endothelial cells were transduced with disabled retrovirus (pLXSN16E6/E7) coding for the human papilloma virus type 16 transforming oncoproteins E6 and E7. Early-passage cells were also stably transfected by electroporation with the pMTV-D305 plasmid vector, in which SV40 large T antigen (SV40 LTAg) mRNA expression is positively regulated by the mouse mammary tumor virus promoter. Expression of E6/E7 mRNA or SV40 LTAg mRNA in cell lines was monitored with the polymerase chain reaction. SV40 LTAg protein expression was detected by immunocytology and Western blot analysis. RESULTS: Human corneal endothelial cells were efficiently infected with disabled retrovirus coding for E6/E7, and seven strains of cells have continued active proliferation for more than 50 population doublings (PD) (< 8 control PD). E6/E7 mRNA was expressed by each cell strain. E6/E7 transformed cells proliferate rapidly and form a monolayer of cells with a high degree of contact inhibition. Transfection with pMTV-D305 is less efficient, and only a single strain was developed. pMTV-D305-transfected endothelial cells (dexamethasone induced) proliferated at a lower rate than E6/E7-transduced cells or cells transfected with a vector (pSV3neo) in which SV40 LTAg is constitutively regulated. In the absence of dexamethasone, the proliferation of pMTV-D305-transfected cells was even slower, but cells continued to produce SV40 LTAg mRNA and protein. The latter results indicated that SV40 LTAg mRNA continued to be synthesized at significant levels in pMTV-D305-transfected cells in the absence of the inducer dexamethasone. CONCLUSIONS: This study suggests that human corneal endothelial cells have a high capacity for proliferation. Thus, cell division is normally controlled in human corneal endothelial cells by poorly characterized, but efficient, mechanisms. Because the E6 and E7 proteins, as well as the SV40 large T antigen, specifically bind to and interfere with the activity of the retinoblastoma (RB) and p53 tumor suppressor proteins, our results suggest that these proteins have critical roles in regulating the proliferation of human corneal endothelial cells.

Antigens, Polyomavirus Transforming↗

A latent form of protein phosphatase 1 alpha associated with bovine heart myofibrils.

The catalytic subunit of the major protein phosphatase associated with bovine cardiac myofibrils was purified to homogeneity. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the enzyme revealed only one band with an apparent molecular weight of 37,000. On gel filtration chromatography, the phosphatase activity and the protein co-eluted as a single peak with an apparent molecular weight of 37,000. The purified enzyme was identified as the catalytic subunit of protein phosphatase 1, as determined by sensitivity to inhibitor 1, inhibitor 2, okadaic acid and by specific immunostaining. Evidence obtained with specific antipeptide antibodies demonstrated that this myofibril protein phosphatase was predominantly the alpha isoform of protein phosphatase 1. The purified catalytic subunit was completely inactive. It was activated by pretreatment with Co2+/trypsin in the presence of high ionic strength. Treatment with trypsin alone did not activate the latent enzyme. The enzyme was also activated by Co2+ or Mn2+ alone but not by Ca2+, Mg2+, Ni2+, Cu2+ or Zn2+. Activation of the enzyme was not reversed by removal of Co2+, but Mn(2+)-activated phosphatase activity was partially reversed when Mn2+ was removed. The catalytic subunit could form a 1:1 complex with inhibitor 2 in vitro. The resulting holoenzyme was also activated by pretreatment with Co2+. Since phosphatase 1 alpha is the major phosphatase associated with cardiac myofibril, it is suggested that it is responsible for the dephosphorylation of myosin and other myofibril phosphoproteins.

Amino Acid Sequence↗

An operator associated with autoregulation of the repressor gene in actinophage phiC31 is found in highly conserved copies in intergenic regions in the phage genome.

Previous reports have suggested that the repressor gene, c, of phiC31 is autoregulated and that likely operators are conserved inverted repeat sequences (CIRs1&2) located just upstream of the promoters, cp1 and cp2. Evidence is now presented that the CIRs 1&2 are indeed binding sites for one of the three inframe, N-terminally different protein isoforms of 42, 54 and 74 kDa produced by the c gene. A cp1-aphII fusion was repressed in a Streptomyces coelicolor A3(2) phiC31 lysogen and characterisation of an operator-constitutive (Oc) mutant showed a single mutation in CIR-1. CIR-1 containing fragments were retarded in electrophoresis gels by the 42 kDa repressor protein isoform and this retardation was inhibited by the addition of competing DNA fragments containing either CIR-1 or CIR-2. Using a combination of Southern blotting and analysis of available DNA sequence we also show that at least 18 copies of the CIRs are present throughout the phiC31 genome. Alignment of 9 CIR sequences showed that 8 contained a perfectly conserved 17 bp core whilst the exception had a single mismatch. The core includes a 16 bp inverted repeat (IR), and is usually part of a more extensive and less highly conserved palindrome. When superimposed on a previously derived transcription map of the early region, the CIRs lie in intergenic regions associated with transcription initiation and/or termination.

Bacteriophages↗

Radiodetoxified endotoxin-induced tolerance alters monocyte but not neutrophil CD11b and CD18 expression in response to lipopolysaccharide.

OBJECTIVES: To test the hypothesis that pretreatment with radiodetoxified endotoxin (RDE) may mitigate the deleterious effects of subsequent infection, in part by modifying leukocyte adhesion receptor expression, and to investigate the cellular mechanisms of endotoxin tolerance induced by RDE. DESIGN: To assess the effect of RDE pretreatment on mortality from bacterial peritonitis, rats were implanted with an intraperitoneal, barium-fecal inoculum at intervals of 0, 1, 3, and 5 days after RDE injection. Experiments were then conducted to test the effect on leukocyte adhesion receptor expression. Two groups of mice received saline solution, and one group, RDE. After 72 hours, one group received saline solution (saline/saline group), the others, lipopolysaccharide (LPS) (saline/LPS and RDE/LPS groups). Peripheral leukocytes were obtained 1 hour after injection and were analyzed for CD11b and CD18 expression by flow cytometry. SETTING: Laboratory animal study. RESULTS: Survival rates were not improved in rats that were pretreated with RDE 0 and 24 hours before inoculum (0% and 7%, respectively). In rats that were pretreated 72 hours and 120 hours before inoculum, 47% (P < .01) and 60% (P < .01) survived, respectively. CD18 expression on polymorphonuclear leukocytes increased twofold in the RDE/LPS (mean +/- SEM, 300.3 +/- 32.9) and the saline/LPS (mean +/- SEM, 360.4 +/- 59.9) groups compared with controls (mean +/- SEM, 176.4 +/- 18.9) (P < .05). CD11b expression on polymorphonuclear leukocytes increased threefold in the RDE/LPS (mean +/- SEM, 91.3 +/- 8.1) and the saline/LPS (mean +/- SEM, 89.8 +/- 11.4) groups compared with controls (mean +/- SEM, 32.1 +/- 1.8) (P < .05). CD18 expression on monocytes decreased in the saline/LPS group (mean +/- SEM, 134.2 +/- 14.2) and was unchanged in the RDE/LPS group (mean +/- SEM, 200.2 +/- 17.2) compared with controls (mean +/- SEM, 217.6 +/- 16.5) (P < .05). CD11b expression on monocytes decreased in the saline/LPS group (mean +/- SEM, 25.8 +/- 2.2) and was unchanged in the RDE/LPS group (mean +/- SEM, 36.4 +/- 0.9) compared with controls (mean +/- SEM, 39.7 +/- 3.9) (P < .05). CONCLUSIONS: Radiodetoxified endotoxin reduces mortality rates from bacterial peritonitis when given at least 72 hours prior to a bacterial inoculum. Tolerance to subsequent LPS challenge is associated with an abrogation of the reduced peripheral monocyte CD11b and CD18 expression observed in native LPS-stimulated mice but is not associated with changes in polymorphonuclear leukocyte CD11b and CD18 expression. The mechanism of the observed RDE-induced monocyte hyporesponsiveness to LPS and its possible protective effect is uncertain and requires further investigation.

Animals↗

Epidermal growth factor, transforming growth factor alpha, transforming growth factor beta, acidic fibroblast growth factor, basic fibroblast growth factor, and interleukin-1 proteins in the cornea.

The purpose of this study was to determine whether epidermal growth factor (EGF), EGF receptor, transforming growth factor alpha (TGF-alpha), transforming growth factor beta (TGF-beta), acidic fibroblast growth factor (acidic-FGF), basic fibroblast growth factor (basic-FGF), and interleukin-1-alpha (IL-1-alpha) proteins were present in cultures of human corneal cells and/or in sections of human corneal tissue. Immunohistochemistry was performed on human corneal sections. Immunofluorescent cell staining was used to evaluate corneal epithelial, stromal fibroblast, and endothelial cells in primary culture. Basic-FGF production was evaluated in culture cells using immunoprecipitation. EGF, TGF-alpha, TGF-beta-1, and IL-1-alpha were detected by immunohistochemistry in cells in all three layers of the cornea. EGF receptor and acidic FGF were detected by immunohistochemistry in epithelial and endothelial cells, but not in stromal fibroblast cells. Differences in distribution of the growth factors were noted within individual layers of the cornea. EGF and basic-FGF proteins were detected in all three predominant cell types of the cornea using immunocytology. IL-1-alpha protein was detected by immunocytology in corneal epithelial and endothelial cells, but not stromal fibroblasts. Immunoprecipitation confirmed the production of basic-FGF in all three cell types. IL-1-alpha protein detection in the corneal stroma by immunohistology, but not by immunocytology in first passage stromal fibroblasts, suggests that IL-1-alpha may localize to the corneal stroma after production by corneal epithelial and/or endothelial cells.

Adult↗

Effect of epidermal growth factor, hepatocyte growth factor, and keratinocyte growth factor, on proliferation, motility and differentiation of human corneal epithelial cells.

We sought to determine the effects of exogenous epidermal growth factor (EGF), heparin-binding EGF (HB-EGF), transforming growth factor alpha (TGF-alpha), single-chain precursor hepatocyte growth factor (SC-HGF), double-chain mature HGF (DC-HGF), and keratinocyte growth factor (KGF) on proliferation, motility, and differentiation of first passage cultures of human corneal epithelial cells in serum-free chemically defined medium. The effect of EGF, HB-EGF, TGF-alpha, SC-HGF, DC-HGF, KGF or combinations of the growth factors on proliferation was measured by counting cells present after 3 weeks of culture and by immunostaining for the cell-cycle-specific nuclear proliferation antigen Ki-67. The effect of the factors on epithelial cell motility was assessed by morphometric analysis of photographs of cells migrating from confluent islands of cells. The effect of growth factors on differentiation of epithelial cells were determined by immunostaining epithelial cell islands for the keratin K3 and by Western blotting for keratin K3. EGF, alone or in combination with KGF and SC-HGF, significantly stimulated motility of epithelial cells at the periphery of confluent islands of cells and induced an elongated cell morphology. TGF-alpha, HB-EGF and DC-HGF produced motility effects similar to EGF. There was diminished proliferation of the migrating cells in response to EGF, HB-EGF, TGF-alpha or DC-HGF, while non-migrating epithelial cells in the center of confluent islands continued to proliferate in response to the growth factors. EGF, HB-EGF, TGF alpha or DC-HGF inhibited expression of the differentiation-related marker keratin K3 in epithelial cells, both at the edge and at the center of the islands. KGF stimulated proliferation of corneal epithelial cells at low density and in confluent islands of cells. KGF did not affect expression of keratin K3 or migration of epithelial cells. SC-HGF had no effect on corneal epithelial cells. These results indicate that the effects of EGF, HB-EGF, TGF-alpha and DC-HGF on corneal epithelial cell proliferation, motility and differentiation vary from those of KGF and SC-HGF. EGF, HB-EGF, TGF-alpha and DC-HGF induced changes in epithelial cell morphology and motility in cells plated at low cell density or in cells located at the edge of a confluent island. Thus, these effects appear to be dependent on the extent of cell-cell contact. The inhibitory effect of EGF, HB-EGF, TGF-alpha or DC-HGF on corneal epithelial cell differentiation, however, is independent of cell density.(ABSTRACT TRUNCATED AT 400 WORDS)

Blotting, Western↗

Intraoperative measurement of Javid shunt flow with transit-time ultrasound.

Transit-time ultrasound methods were used to measure blood flow in 37 patients undergoing carotid endarterectomy. Internal carotid flow before (ICFbef) and after (ICFaft) endarterectomy was measured with a 6 mm perivascular probe, and Javid shunt flow (SF) was measured with a clamp-on probe. For the entire group ICFbef averaged 117 +/- 67 ml/min and ICFaft was 173 +/- 67 ml/min. Shunt flow averaged 123 +/- 51 ml/min. The differences between ICFbef and ICFaft and between SF and ICFaft were significant (ANOVA, p < 0.01) but the difference between ICFbef and SF was not. The relationship between ICFbef and SF appeared to define two groups of patients. Those in whom SF was greater than ICFbef (SF > ICFbef) had more stenosis evident on preoperative arteriograms (64.7% +/- 14.55% maximum single diameter stenosis) and a greater average increase in ICF (151% +/- 159%) than those with SF < or = ICFbef (43.3% +/- 20.9% stenosis and 34% +/- 54% increase in ICF), suggesting that the relationship between SF and ICFbef defines groups with different hemodynamic responses. The similarity between SF and ICFbef indicates that Javid shunt flow offers adequate protection from cerebral ischemia. A practical benefit of the shunt clamp-on flow probe is the ability afforded to recognize shunt occlusions.

Anastomosis, Surgical↗

Superiority of aztreonam/clindamycin compared with gentamicin/clindamycin in patients with penetrating abdominal trauma.

There were 73 evaluable patients entered into a prospective, double-blinded trial comparing aztreonam/clindamycin (A/C) to gentamicin/clindamycin (G/C) for the prevention of infection after penetrating abdominal trauma. Aztreonam was administered at a dosage of 2 g every 8 hours and gentamicin at 5 mg/kg for the first 24 hours and then adjusted by serum monitoring to a peak of 6 to 8 micrograms/mL and a trough of less than 2 micrograms/mL; all patients received 900 mg of clindamycin every 8 hours. Patients with colon wounds received 4 days of antibiotics, and the remaining patients received a 24-hour course. Gunshot wounds occurred in 69% of patients: 74% of all patients had some hollow viscus injury, and 26% had only solid viscus injury. The groups were well matched according to abdominal trauma index, percentage with colon injury, and transfusion requirements. Failures occurred in eight patients (11%): two wound infections, five intra-abdominal infections, and one case of necrotizing fasciitis. Seven infections occurred in 36 (19%) G/C patients compared with 1 in 37 (3%) A/C patients (p < 0.03). The hospital stay was 12 +/- 11 days for G/C patients and 8 +/- 7 for A/C patients (p < 0.12). The superiority of the A/C regimen may be partially attributable to relative underdosing of gentamicin (approximately half of the patients had inadequate levels after 24 hours) combined with a favorable pharmacokinetic profile (significantly prolonged half-life) of aztreonam in this clinical setting.

Abdominal Injuries↗