Biomedical subjects

S E Wilson

Publications and source records attributed to S E Wilson.

At least 109 records · Page 6Linked to original sources

PubMed1998

Elder abuse and neglect: the emergency medicine perspective.

The diagnosis of elder abuse and neglect is difficult to accomplish, making intervention elusive, primarily because to date there is no set definition of either abuse or neglect. This paper, written primarily from the American viewpoint, addresses definitions; assessment and diagnosis; aetiology of abuse; intervention; prevention and management; ethical and legal considerations; elder abuse and the emergency physician; and future goals.

Aged↗

PubMed1998

Characterization of a soluble KGF receptor cDNA from human corneal and breast epithelial cells.

PURPOSE: Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family FGF-7. It exhibits potent mitogenic activity for epithelial cells, including corneal and mammary epithelial cells. A messenger RNA has been reported that is generated by alternative splicing of bek that putatively codes only for the extracellular ligand-binding domain of KGF receptor (soluble KGF receptor). In the present study, the expression of the mRNA coding for this alternative bek transcript was examined and the corresponding protein characterized. METHODS: Alternative messenger RNA transcripts were detected in various cell lines or tissues using reverse transcription-polymerase chain reaction (RT-PCR) and RNase protection assay. NIH/3T3 fibroblast cells and 293 kidney embryonic epithelial cells were stably transfected with soluble KGF receptor cDNA and transmembrane KGF receptor cDNA. Soluble KGF receptor protein was produced using a baculovirus-insect expression system. Soluble KGF receptor protein was detected using western and dot blot analyses. Binding assays and cross-linking labeling were used to determine the affinity and specificity of soluble KGF receptor. A mitogenic assay was performed to examine the function of the soluble KGF receptor. RESULTS: The soluble KGF receptor mRNA was primarily expressed in epithelial cells, including cells from the cornea and breast. Cross-linking labeling and affinity-binding assays with 125I-KGF showed that the soluble KGF receptor bound KGF (FGF-7) but not FGF-1 or FGF-2. Soluble KGF receptor was detected in the culture medium of cells stably transfected with soluble KGF receptor cDNA but not with transmembrane KGF receptor cDNA, suggesting that the soluble receptor was generated by mRNA splicing and probably not by proteolysis or posttranslational processing. Soluble KGF receptor inhibited KGF binding to transmembrane KGF receptor and DNA synthesis in BALB/MK epidermal keratinocytes in response to KGF, suggesting that soluble KGF receptor expression could provide a mechanism for the cell to downregulate responses to KGF. CONCLUSIONS: A truncated soluble KGF receptor expressed in corneal and other epithelial cells probably functions to downregulate the response of the cell to KGF.

3T3 Cells↗

PubMed1998

Bone morphogenic proteins 2 and 4 and their receptors in the adult human cornea.

PURPOSE: To examine the expression of transforming growth factor family members bone morphogenic proteins 2 and 4 (BMP2, BMP4), their receptor mRNAs, and BMP2 and BMP4 proteins in the cells of the human cornea. The effects of BMP2 and BMP4 on corneal fibroblast proliferation and apoptosis were also examined. METHODS: Reverse transcription-polymerase chain reaction, immunoprecipitation, and western blot analysis were used to examine mRNA and protein expression in cultured human corneal cells. Immunocytochemistry was applied to examine protein localization in fresh frozen human cornea cells. Stimulation and inhibition of nuclear factor-kappaB (NF-kappaB) activation was evaluated by gel shift assay. Apoptosis was examined using trypan blue exclusion, laddering of DNA, CPP32 assay, and transmission electron microscopy. Proliferation was monitored by counting cells. RESULTS: BMP2 and BMP4 mRNAs and proteins were expressed in cultured human corneal epithelial cells, keratocytes, and corneal endothelial cells. BMP2 and BMP4 were detected in each major corneal cell type in fresh frozen human cornea. BMP receptor IA, IB, and II mRNAs were also detected in cultured human corneal epithelial cells, keratocytes, and endothelial cells. BMP2 and BMP4 stimulated activation of NF-kappaB. Actinomycin D and SN50 peptide, but not SN50M control peptide, inhibited NF-kappaB activation in response to BMP2 or BMP4. BMP2 and BMP4 stimulated apoptosis of corneal fibroblast cells when NF-kappaB activation was inhibited with the nonselective inhibitor actinomycin D or selective inhibitor SN50. The nonsteroidal anti-inflammatory agents ketorolac tromethamine and diclofenac sodium augmented the effect of BMP2 on corneal fibroblast apoptosis. BMP2 and BMP4 both stimulated proliferation of corneal fibroblast cells in the absence of inhibitors of NF-kappaB activation. CONCLUSIONS: BMP2, BMP4, and their receptors are expressed in the cells of the adult human cornea. The functions regulated by these cytokines may include keratocyte proliferation and apoptosis.

Adult↗

PubMed1998

The management of skin and skin structure infections in children, adolescents and adults: a review of empiric antimicrobial therapy.

This article reviews the diagnosis and management of mild-to-moderate skin and skin structure infections in children, adolescents and adults in a general practice setting. Therapies reviewed are those in current use: penicillins; beta-lactamase stable penicillins, including flucloxacillin, oxacillin, and amoxicillin-clavulanate; oral quinolones; macrolides; and oral cephalosporins. Consideration is given to duration of therapy, side-effect profile and compliance.

Adolescent↗

PubMed1998

Selective targeting and photodynamic destruction of intimal hyperplasia by scavenger-receptor mediated protein-chlorin e6 conjugates.

BACKGROUND: Photosensitizers, such as Photofrin II or Chloroaluminum-sulfonated phthalocyanine accumulate at sites of arterial injury. We have exploited this property to develop a model of photodynamic therapy (PDT) for intimal hyperplasia. The fluorescent probe [maleylated-bovine serum albumin (mal-BSA) conjugated with Texas-red] can be selectively targeted to intimal macrophages and smooth muscle cells recruited during formation of hyperplasia via a receptor-mediated mechanism. METHODS: In this study, the photosensitizer chlorin e6 (Cle6) was conjugated to mal-BSA in a rat model of intimal hyperplasia, then tested the efficacy of the ligand conjugation to photosensitizer (mal-BSA/Cle6) in PDT of intimal hyperplasia. Arterial wall injury was produced by a balloon catheter pulled through the abdominal aorta of the rat to create a model of intimal hyperplasia. Fluorescent compounds were injected two weeks after injury. RESULTS: Four hours after injection, the intensity of fluorescence achieved with injection of mal-BSA/Cle6 was higher for intimal hyperplastic lesions as compared to control areas. BSA-Cle6 unconjugated did not demonstrate such delivery. Two weeks after balloon injury, the injured aorta was irradiated externally with an argon pumped dye laser four hours following the photosensitizer injection. We employed two total radiant exposures: 20 J/cm2 and 40 J/cm2. Forty-eight hours after PDT, the arteries were examined histologically. Intimal hyperplastic cells were significantly reduced by PDT in the mal-BSA/Cle6 injected group (40-100%) versus the Cle6 group (0-20%). CONCLUSIONS: Mal-BSA/Cle6 is taken up efficiently by a scavenger pathway, localizes in areas of intimal hyperplasia, and functions as a photosensitizer for PDT.

Animals↗

PubMed1997

Biomechanics of osteoporosis and vertebral fracture.

The ability of the spine to carry load depends on the structural capacity of the vertebrae and on the loading conditions that arise from activities of daily living or trauma. The ratio of the load on the spine to the failure load of the bone is called the factor of risk, a value that indicates whether fracture is likely during a given activity. A high factor of risk can result from weak bone that has a low failure load or from a risk activity that generates a large force. The failure load of the vertebral body depends on the density and architecture of the trabecular bone and on the shape, size, and organization of the vertebral body. Spine bone mineral density determined by dual-energy x-ray absorptiometry correlates strongly with the compressive failure load and therefore should be a convenient and specific indicator of the compressive strength of the vertebrae in vivo. The magnitude of a load applied to the spine depends on the specific activity. Bending and lifting activities generate loads on the spine that exceed the failure load of vertebrae with very low bone mineral density. Biomechanical indications for prevention of age-related fractures point to the need to strengthen bone by maintaining or increasing density and the need to lower the magnitude of forces applied to the spine in the elderly by avoiding such risk activities as lifting.

Aged↗

PubMed1997

HIV type 1 envelope glycoprotein 120 carboxy-terminal peptide-induced human T cell lines selectively suppress heterogeneous proliferative T cell responses to soluble antigens.

It has been proposed that the highly conserved human immunodeficiency virus type 1 (HIV-1) envelope gp120 carboxy-terminal sequence, TKAKRRVVEREKR (CT120), may represent a functional mimic of the human leukocyte antigen (HLA) class II DR beta-chain third hypervariable region (HVR3) sequence motif located at position 69-81. Presentation of this potentially pathogenic fragment by HLA class I and/or II molecules, in a manner analogous to the indirect pathway of allorecognition, may induce both widespread cellular activation and also break self-tolerance, resulting in the selective and progressive anti-self HLA class II-directed immune suppression, which is a central feature of HIV-1 infection and the associated acquired immune deficiency syndrome (AIDS). To investigate the functional role of the HIV-1 gp120 C-terminal fragment T cell lines (TCLs) were raised from three healthy HIV-1-seronegative subjects at low risk of HIV-1 exposure, by repeated stimulation with a short synthetic 13-mer CT120 peptide in vitro. Graded concentrations (10[3] to 5 x 10[4]) of CT120 TCLs suppressed the primary 6-day proliferation of autologous PBMCs in response to the soluble antigens tetanus toxoid (TT) and purified protein derivative (PPD). In contrast, CT120 TCLs demonstrated no suppressive effect on 3-day phytohemagglutinin (PHA), concanavalin A (ConA), and pokeweed mitogen (PWM) mitogenic responses. Fractionation of CT120 TCLs into highly purified CD4+ and CD8+ T cell subsets demonstrated that the CD8+ T cell fraction mediated the suppressor effector function. HLA restriction analysis revealed a complex pattern as both anti-HLA class II DR and anti-HLA class I (A, B, C) MAbs inhibited proliferation of oligoclonal CD8+ CT120 TCLs. Strategies aimed at specifically inhibiting such putative immunopathogenic HIV-1-encoded T cell epitopes may be an important consideration for development of future HIV-1 immunotherapy.

Adult↗

PubMed1997

The bi-loop, a new general four-stranded DNA motif.

The crystal structure of the cyclic octanucleotide d contains two independent molecules that form a novel quadruplex by means of intermolecular Watson-Crick A.T pairs and base stacking. A virtually identical quadruplex composed of G.C pairs was found by earlier x-ray analysis of the linear heptamer d(GCATGCT), when the DNA was looped in the crystal. The close correspondence between these two structures of markedly dissimilar oligonucleotides suggests that they are both examples of a previously unrecognized motif. Their nucleotide sequences have little in common except for two separated 5'-purine-pyrimidine dinucleotides forming the quadruplex, and by implication these so-called "bi-loops" could occur widely in natural DNA. Such structures provide a mechanism for noncovalent linking of polynucleotides in vivo. Their capacity to associate by base stacking, demonstrated in the crystal structure of d(GCATGCT), creates a compact molecular framework made up of four DNA chains within which strand exchange could take place.

Base Composition↗

PubMed1997

Prevalence and associations of abdominal aortic aneurysm detected through screening. Aneurysm Detection and Management (ADAM) Veterans Affairs Cooperative Study Group.

BACKGROUND: Independent risk factors for abdominal aortic aneurysm (AAA) have not been clearly defined in multivariable analyses of large patient populations. OBJECTIVE: To identify factors that are independently associated with AAA and to determine the prevalence of previously unrecognized AAA in defined demographic and risk groups. DESIGN: Cross-sectional screening study. SETTING: 15 Department of Veterans Affairs medical centers. PARTICIPANTS: 73451 veterans who were 50 to 79 years of age and had no history of AAA. MEASUREMENTS: The results of ultrasonographic screening for AAA and a prescreening questionnaire were analyzed using multiple logistic regression. RESULTS: An AAA of 4.0 cm or larger was detected in 1031 participants (1.4%). Smoking was the risk factor most strongly associated with AAA; the odds ratio (OR) for AAAs of 4.0 cm or larger compared with normal aortas (infrarenal aortic diameter < 3.0 cm) was 5.57 (95% CI, 4.24 to 7.31). The association between smoking and AAA increased significantly with the number of years of smoking and decreased significantly with the number of years after quitting smoking. The excess prevalence associated with smoking accounted for 78% of all AAAs that were 4.0 cm or larger in the study sample. Female sex (OR, 0.22 [CI, 0.07 to 0.68]), black race (OR, 0.49 [CI, 0.35 to 0.69]), and presence of diabetes (OR, 0.54 [CI, 0.44 to 0.65]) were negatively associated with AAA. A family history of AAA was positively associated with AAA (OR, 1.95 [CI, 1.56 to 2.43]) but was reported by only 5.1% of participants. Other independently associated factors included age, height, coronary artery disease, any atherosclerosis, high cholesterol levels, and hypertension. CONCLUSIONS: Abdominal aortic aneurysm is associated with multiple factors. Smoking was the risk factor most strongly associated with AAA and may be responsible for most clinically important cases of previously undiagnosed AAA.

Aged↗

PubMed1997

Tear hepatocyte growth factor (HGF) availability increases markedly after excimer laser surface ablation.

Tear cytokines and growth factors are likely to modulate the wound healing process following corneal epithelial injury. Hepatocyte growth factor (HGF) is a paracrine mediator of epithelial proliferation, motility, and differentiation that is produced by keratocytes and the lacrimal gland. Tear samples were collected preoperatively and one, two, and seven days postoperatively in eyes undergoing excimer laser surface ablation [photorefractive keratoplasty (PRK) or phototherapeutic keratoplasty (PTK)]. Tear HGF concentration was measured with a sensitive ELISA assay. Tear HGF production was calculated using the tear flow rate in the collection capillary and HGF concentration. Although the instantaneous concentration of HGF in tears decreased significantly in the days following PRK, a large increase in tear flow resulted in a marked increase in HGF bioavailability. The heparin-binding characteristics of HGF would result in increased binding to glycosaminoglycans and other heparin-like matrix components and, therefore, increased growth factor availability to the cognate recptor. This is the first report documenting changes in tear film HGF production. HGF may have an important function in maintenance and wound healing of the ocular surface epithelium since HGF is present in the normal tear film and the HGF secretion rate increases markedly in parallel with aqueous tear production following corneal surgical injury.

Enzyme-Linked Immunosorbent Assay↗

PubMed1997

Herpes simplex virus type-1 infection of corneal epithelial cells induces apoptosis of the underlying keratocytes.

The purpose of this study was to determine whether primary corneal infection with Herpes simplex virus (HSV)-1 induces keratocyte apoptosis in the rabbit. New Zealand white rabbit eyes were inoculated with HSV-1 strain 17 Syn+. Rabbits that developed slit lamp signs of epithelial infection were killed between 12 and 120 hr post infection. One cornea of each animal was fresh-frozen for TUNEL assay to detect DNA fragmentation in situ. The other cornea was fixed for transmission electron microscopy (TEM). Mechanical scrape wounded rabbit corneas were included as positive controls. DNA fragmentation consistent with apoptosis was detected in anterior keratocytes of corneas at 18, 24, and 48 hr after primary infection with HSV-1 and 2 hr after an epithelial scrape, but not in unwounded control corneas. Electron microscopic evidence of keratocyte apoptosis that included chromatin condensation, chromatin fragmentation, and cellular blebbing with formation of membrane bound cell fragments was detected in mechanical scrape wounded corneas and infected rabbit corneas at 12, 18, 24, 48, and 120 hr after infection, but not in unwounded control corneas. This study suggests that anterior stromal keratocyte apoptosis occurs following primary HSV-1 infection of the corneal epithelium. Previous studies have demonstrated that corneal epithelial scrape wounds induce apoptosis in the underlying keratocyte cells. We hypothesize that soluble mediators released by epithelial injury mediate anterior keratocyte apoptosis and that one of the physiologic functions of this epithelial-stromal apoptosis system is to limit viral extension.

Animals↗

PubMed1997

Fuchs' corneal endothelial cells transduced with the human papilloma virus E6/E7 oncogenes.

We sought to develop corneal endothelial cell cultures with extended lifespan from corneas with Fuchs' dystrophy. Descemet's-endothelial cell explants from histology confirmed recipient corneas of two patients with Fuchs' dystrophy were cultured. After a small number of corneal endothelial cells with irregular, endothelial morphology migrated from the explants onto the culture plate, the cells were transduced with a disabled retrovirus (pLXSN16E6/E7) coding for the human papilloma virus type 16 transforming oncoproteins E6 and E7. Expression of E6/E7 mRNA in the cell cultures with extended lifespan was monitored by RT-PCR. In vitro labeled cellular protein patterns of the Fuchs' E6/E7 cell cultures with extended lifespan were compared with those from normal human corneal endothelial E6/E7 cell cultures with extended lifespan using two-dimensional gel electrophoresis. Two endothelial cell cultures with extended lifespan were derived from Fuchs' corneas. The morphology of the Fuchs' cells expressing E6 and E7 was similar to that of normal corneal endothelial cells expressing E6 and E7. Surprisingly, the rate of proliferation of Fuchs'-derived cells was similar to that of normal endothelial cells transduced with E6/E7. Proliferation of each Fuchs' cell culture with extended lifespan continued for over 30 population doublings. There were limited quantitative differences in the two-dimensional gel electrophoretic protein patterns of the Fuchs'-derived and normal endothelial cell cultures with extended lifespan, respectively. Retroviral integration is dependent on cell proliferation. Thus, cells that migrated from the Fuchs' Descemet's explants were undergoing at least limited in vitro proliferation when the retroviral vector coding for E6/E7 integrated. Fuchs' corneal endothelial cells expressing E6 and E7 had similar proliferation, cellular morphology, and two-dimensional gel protein electrophoretic patterns to normal corneal endothelial cells expressing the same oncoproteins.

Cell Division↗

PubMed1997

Apoptosis in the cornea: further characterization of Fas/Fas ligand system.

This study was performed to further characterize expression and function of the Fas/Fas ligand system in the cornea. Specifically, these experiments examined (1) the effect of genetic inactivation of Fas or Fas ligand genes on keratocyte apoptosis in response to corneal epithelial wounding, (2) whether cultured human corneal epithelial and endothelial cells are competent to undergo apoptosis in response to Fas activation, (3) expression of membrane bound and soluble Fas and Fas ligand in corneal cells, and (4) the effect of IL-1 on expression of Fas and Fas ligand in corneal fibroblasts. Keratocyte apoptosis in response to corneal epithelial scrape detected by TUNEL assay and transmission electron microscopy was significantly decreased, but not eliminated, in Fas ligand -/- mice compared with control +/+ mice. There was also a decrease in Fas -/- mice that did not reach statistical significance. Thus, while the Fas/Fas ligand system is likely involved in regulating keratocyte apoptosis in response to epithelial wounding, systems with redundant function probably also modulate this response. Activation of the Fas receptor triggered death with ultrastructural changes characteristic of apoptosis in corneal epithelial and endothelial cells in culture. Since these cell types express both Fas and Fas ligand in vivo, systems must be in place to prevent uncontrolled activation via autocrine ligand-receptor interaction. Messenger RNAs coding for both membrane bound and soluble splicing variants of Fas were expressed in each corneal cell type, suggesting that soluble Fas production could be one mechanism to antagonize membrane bound Fas activation. Soluble Fas ligand protein was expressed in wounded ex vivo corneal epithelium, providing a mechanism for Fas ligand from epithelium to mediate keratocyte apoptosis. IL-1, however, also stimulated corneal fibroblasts to express Fas ligand mRNA and protein. Therefore, an alternative mode for epithelial injury to trigger keratocyte apoptosis may be by release of IL-1, subsequent induction of Fas ligand in keratocytes, and apoptosis mediated by autocrine mechanisms.

Animals↗

PubMed1997

Healing mechanisms of high-porosity PTFE grafts: significance of transmural structure.

A high-porosity structure facilitates endothelialization of polytetrafluoroethylene (PTFE) grafts. The mechanism for endothelial coverage, however, has been controversial. This study was designed to clarify the healing mechanisms of high-porosity PTFE grafts. Four types of PTFE grafts (n = 48) were studied after implantation in both carotid and femoral arteries of dogs. The grafts were standard (ST) PTFE [mean internodal distance (MID): 30 microm]; high-porosity (HP) PTFE (MID 90 microm), composite porosity (CP) PTFE (MID: inner layer, 90 microm; outer layer, 30 microm); and polyurethane-coated high-porosity (PCHP) grafts which had the outer surface covered with nonporous polyurethane. Patency rates at 18 weeks were ST 6/12, HP 8/12, CP 6/12, and PCHP 3/12 (P = 0.290). The rates of endothelialization (%, mean +/- SD) in the patent grafts were ST 25 +/- 7, HP 75 +/- 20,* CP 57 +/- 15,* and PCHP 17 +/- 5 (*P < 0.05 vs ST or PCHP). Rich transmural tissue incorporation was observed in the HP grafts. In contrast to the HP grafts, PCHP grafts had no outer tissue ingrowth, inner tissue incorporation was scant, and anastomotic intimal hyperplasia was pronounced. The edges of pannus ingrowth in the PCHP grafts were irregular, such that the anchoring of pannus was weak and easily detachable. Well-developed endothelial cells were observed in the HP and CP grafts, but nonendothelialized areas always occurred in the center of the grafts. Capillary openings were noted in the HP grafts; however, their number was small (0-8/graft) on electron microscopy and did not account for the degree of endothelialization observed. We conclude that the principal mechanism for endothelialization of PTFE grafts is ingrowth from the anastomoses rather than transmural endothelialization, even in high-porosity grafts. Transmural fibrocapillary incorporation of PTFE vascular grafts provides a key supporting structure essential to the progression and attachment of endothelial ingrowth from the anastomoses.

Animals↗

PubMed1997

Late disruption of Dacron aortic grafts.

Aneurysmal degeneration, or complete disruption of Dacron grafts (as opposed to anastomotic complications such as pseudoaneurysms), are not expected by vascular surgeons. We have noted two such cases. A 65-year-old male who had an aortobifemoral, double-velour Dacron graft in 1980, presented in 1995 with a large, pulsatile mass in the right lower quadrant, caused by disruption of the mid-portion of the right limb of the Dacron graft. In a second case, a 68-year-old man had a Dacron aortobifemoral graft placed in 1968 which developed diffuse aneurysmal defects, noted clinically in 1987. Both patients had successful graft replacement. A review of the literature indicates that this complication, although unusual, has been noted periodically. Between 1970 and 1996, we identified 11 case reports of aortic Dacron graft rupture, including knitted Dacron (4), double velour (3), woven (1), knitted thin wall (1), and unspecified Dacron grafts (2). An inquiry to the FDA disclosed another 68 cases of Dacron graft failure in addition to those reported in the surgical literature. We present these cases to alert vascular surgeons of the possibility of Dacron graft degeneration, as late as 19 years after implantation. Diagnosis of the complication is readily apparent by clinical examination and imaging studies, which display an aneurysm of the graft remote from the anastomoses.

Aged↗

PubMed1997

Computed tomography-assisted management of splenic trauma.

BACKGROUND: In patients who have suffered an injury to the spleen, preservation of the organ is of the utmost importance. To assist in management, contrast-enhanced computed tomography (CT) has been used. We reviewed our experience with a protocol for nonoperative management of splenic trauma based on CT grading of the injury. METHODS: During the initial period of the study, 50 CT examinations for blunt abdominal trauma in adults were reviewed by staff radiologists for evidence of splenic injury. The radiologists, blinded to clinical management decisions, graded the CT studies as "A" if there was a subcapsular hematoma or capsular disruption, "B" if there was a parenchymal injury not extending into the hilum, or "C" if there was deep laceration of fracture of the hilum. Following confirmation of the accuracy and reproducibility of the grading scale, the splenic trauma management protocol was instituted, in which nonhilar injuries were managed nonoperatively. RESULTS: In the initial assessment, patients managed nonoperatively had shorter hospital stays and received fewer blood transfusions than those undergoing operation. Among 30 patients subsequently enrolled in the protocol, those treated nonoperatively remained in the hospital for fewer days than those treated surgically. Again, fewer units of blood and platelets were used in the nonoperative group. Institution of the protocol decreased the incidence of celiotomy. CONCLUSIONS: The severity of splenic trauma evident on CT staging guides safe nonoperative management. Patients not suffering injury to the splenic hilum (A and B scores) can be managed without operation, resulting in shorter hospital stays and fewer blood products used.

Abdominal Injuries↗

PubMed1997

Meta-analysis of the clinical outcome of carbapenem monotherapy in the adjunctive treatment of intra-abdominal infections.

BACKGROUND: The carbapenems, a class of beta-lactam antimicrobials with efficacy against both aerobic and anaerobic organisms, have demonstrated potential as monotherapeutic regimens in the treatment of serious intra-abdominal infections. Clinical trials have been conducted in the past decade to compare carbapenem monotherapy versus combinations of antibiotic therapy. We report here a meta-analysis of 10 such trials. DATA SOURCES: An 11-year Medline search (from 1985 through 1996) of the English-language literature identified clinical trials that compared the outcomes of carbapenem monotherapy, either imipenem/cilastatin or meropenem, versus another antibiotic regimen in intra-abdominal infections in human subjects. Ten randomized, prospective trials were found, with a total of 1,227 clinically evaluable patients. A meta-analysis of these clinical trials was performed to determine the difference in clinical outcomes between carbapenem monotherapy versus other antibiotic regimens. We found a difference in response rates of -1.6% (95% confidence interval [CI] -5.7% to 2.5%) and a response ratio of 0.99 (95% CI, 0.90 to 1.09), indicating no statistical significant difference. CONCLUSIONS: A meta-analysis of 10 clinical trials from 1985 through 1996 has revealed no statistical significant difference in clinical response between carbapenem monotherapy and combinations of antibiotic therapy in intra-abdominal infections. We noted, however, that the earlier studies reported more favorable response ratios for carbapenems than later publications. This may have been due to the selection of less effective comparators in earlier studies. We conclude that carbapenem monotherapy is as effective as combinations of antimicrobials for the treatment of intra-abdominal infections.

Abdomen↗

PubMed1997

Unilateral keratoconus. Incidence and quantitative topographic analysis.

OBJECTIVE: This study was designed to determine the incidence of unilaterality in a population of patients with clinical keratoconus and to compare quantitative descriptors of topography between affected corneas from patients with unilateral keratoconus and corneas of patients with bilateral disease. DESIGN: Retrospective clinical study with new evaluation of some patients. PARTICIPANTS: One hundred sixty-four patients from the University of Texas South-western Medical Center and Wills Eye Hospital who were diagnosed to have moderate-to-advanced keratoconus on the basis of characteristic topographic patterns associated with corneal thinning. INTERVENTION: Corneal topography was evaluated in both eyes of each patient. MAIN OUTCOME MEASURES: Quantitative descriptors of corneal topography were compared between 5 affected corneas of patients with unilateral keratoconus (combined cases from University of Texas Southwestern, LSU Eye Center, and Wills Eye Hospital) and 15 corneas of patients with moderate-to-advanced bilateral keratoconus (1 cornea from each patient). Indices selected for statistical analysis were the Keratoconus Predication Index (KPI), Surface Asymmetry Index (SAI), and Surface Regularity Index (SRI). RESULTS: Three (1.83%) of 164 patients with moderate-to-advanced keratoconus had no topographic evidence of keratoconus in the opposite eye. There were no statistically significant differences in KPI, SRI, or SAI values between the affected corneas of patients with unilateral and bilateral keratoconus. Over a period of 4 years of observation, signs of keratoconus in the previously normal eye developed in a patient with unilateral keratoconus. CONCLUSIONS: The authors found no differences in the quantitative descriptors of corneal topography between corneas with keratoconus from unilateral and bilateral cases. The authors' results suggest that the incidence of "unilateral" keratoconus is very low. Patients initially diagnosed with unilateral keratoconus, if observed for a sufficient period, commonly had signs of keratoconus develop in the opposite eye. The possibility that all cases of unilateral keratoconus may eventually become bilateral cannot be excluded. Therefore, refractive surgical procedures should not be performed on apparently normal corneas when keratoconus is detected in the opposite eye.

Cornea↗