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Biomedical subjects

V Sanders

Publications and source records attributed to V Sanders.

At least 19 recordsLinked to original sources

Hospital-acquired pneumonia: microbiological data and potential adequacy of antimicrobial regimens.

Adequate antimicrobial therapy is a main approach employed to decrease the mortality associated with hospital-acquired pneumonia (HAP). All methods that optimise empirical treatment without increasing antibiotic selective pressure are relevant. Categorisation of patients according to HAP time of onset, severity and risk factors (American Thoracic Society (ATS) classification) or duration of mechanical ventilation and prior antibiotics (Trouillet's classification) are two such methods. The aim of this study was to catagorise patients with HAP according to these classifications and to determine the frequency of resistant pathogens and the most adequate antimicrobial regimens in each group. A total 124 patients with bacteriologically proven HAP were studied. The ATS classification categorised patients by increasing frequency of resistant pathogens from 0-30.3%. The ATS empirical antibiotic recommendations appeared valid but proposed combinations including vancomycin for 72.5% of patients. Trouillet's classification categorised patients into four groups with a frequency of resistant pathogens from 4.9-35.6%. Vancomycin was proposed for 48.5% of patients. The American Thoracic Society classification appears to be more specific than Trouillet's for predicting the absence of resistant causative pathogens in hospital-acquired pneumonia but could lead to a greater use of vancomycin. Stratification combining the two classifications is an interesting alternative.

Aged↗

Pupillary capture of the optic in secondary piggyback implantation.

Two patients who received a minus-power intraocular lens implanted as a secondary piggyback to correct pseudophakic myopia experienced pupillary optic capture following dilation in the early postoperative period. Both cases were successfully managed by pressing the optic back into the ciliary sulcus and constricting the pupil with pilocarpine.

Aged↗

Mortality due to ventilator-associated pneumonia: impact of medical versus surgical ICU admittance status.

PURPOSE: The purpose of this study was to compare the prognosis of medical versus surgical patients developing ventilator-associated pneumonia (VAP). MATERIALS AND METHODS: An observational cohort study included 125 consecutive patients exhibiting VAP. Incidence of death occurred at two different times: during intensive care unit (ICU) stay and during hospital stay. RESULTS: Eighty-seven patients were included in the medical group and 38 in the surgical group. On ICU admission and at the time of VAP onset, most collected data, such as demographic parameters, severity of underlying diseases, and current illness, risk factors forVAP development andVAP characteristics were similar in the two groups. Mortality rates during ICU and hospital stays were not significantly different in medical (49%, 56%) and surgical (55%, 61%) groups. In multivariate logistic regression model adjusting for main factors of VAP mortality, surgical admittance status demonstrated no significant impact on mortality assessed during ICU stay (AOR = 1.6; 0.6 - 4.3 CI) and during hospital stay (AOR = 1.6; 0.6 - 4.2 CI). CONCLUSIONS: In this series, after adjustment for mortality confounding factors, medical versus surgical admittance status was not a significant determinant of VAP mortality.

Aged↗

Amelioration of neurotoxic effects of HIV envelope protein gp120 by fibroblast growth factor: a strategy for neuroprotection.

Approximately two thirds of patients with human immunodeficiency virus encephalitis (HIVE) show cognitive impairment and neurodegeneration, while one third are cognitively unimpaired and their neuronal populations are preserved. Thus, it is possible that these individuals might have the capacity to produce neurotrophic factors capable of protecting neurons against the deleterious effects of HIV. In this context, the main objective of this study was to determine whether fibroblast growth factor 1 (FGF1) is protective against HIV. For this purpose levels of FGF1 immunoreactivity were determined in the frontal cortex of 35 AIDS cases subdivided into 4 groups according to the presence or absence of HIVE and neurodegeneration. In cases without both HIVE and neurodegeneration, mild to moderate levels of FGFI immunoreactivity were observed in pyramidal neurons, while in cases with HIVE but without neurodegeneration, levels were significiantly elevated. In contrast, individuals with both HIVE and neurodegeneration showed low levels of neuronal FGF1 immunoreactivity. Furthermore, studies in primary human neuronal cultures treated with the HIV envelope protein-gp120 in the presence or absence of FGF1 showed that FGF1 was protective against gpl20 neurotoxicity in a dose-dependent manner. Taken together, these results support the notion that upregulation of certain neurotrophic factors, such as FGF1, might protect the central nervous system from the neurotoxic effects of HIV.

AIDS Dementia Complex↗

Interlenticular opacification: clinicopathological correlation of a complication of posterior chamber piggyback intraocular lenses.

PURPOSE: To present a clinicopathological correlation of 2 pairs of piggyback posterior chamber intraocular lenses (PC IOLs) explanted because of opacification between the lens optics. SETTING: Gayton Health Center, Eyesight Associates of Middle Georgia, Warner Robins, Georgia, and Center for Research on Ocular Therapeutics and Biodevices, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: Two pairs of piggyback AcrySof lenses were explanted from 2 patients with significant visual loss related to opacification between the optics. They were submitted for pathological analysis. Gross and histopathological examinations were performed, and photomicroscopy was used to document the results. RESULTS: Gross examination showed accumulation of a membrane-like white material between the lenses. Histopathological examination revealed that the tissue consisted of retained/proliferative lens epithelial cells (bladder cells or pearls) mixed with lens cortical material. CONCLUSION: Piggyback PC IOLs were explanted in 2 cases because of a newly described complication, interlenticular opacification. Three surgical means may help prevent this complication: meticulous cortical cleanup, especially in the equatorial region; creation of a relatively large continuous curvilinear capsulorhexis to sequester retained cells peripheral to the IOL optic within the equatorial fornix; insertion of the posterior IOL in the capsular bag and the anterior IOL in the ciliary sulcus to isolate retained cells from the interlenticular space.

Acrylic Resins↗

Damage and repair of DNA in HIV encephalitis.

Neuronal damage and dementia are common sequelae of HIV encephalitis. The mechanism by which HIV infection of CNS macrophages results in neuronal damage is not known. We examined the brains from 15 AIDS autopsies (8 with HIV encephalitis and 7 without) and 4 non-infected control autopsies for the presence of DNA strand breaks, for associated changes in the expression of the DNA repair enzymes KU80 and Poly (ADP-ribose) polymerase (PARP), and for accumulation of amyloid precursor protein (APP). Abundant DNA damage was observed with terminal transferase-mediated dUTP nick end-labeling (TUNEL), however, there was no morphologic evidence of significant neuroglial apoptosis. The DNA repair enzyme KU80 was immunocytochemically detectable in neuronal and glial cells in autopsy brains from patients with and without HIV encephalitis; however, in cases with HIV encephalitis the staining was more prominent than in the infected or non-infected controls without encephalitis. There was no difference in KU80 immunostaining in oligodendroglia from autopsies with and without encephalitis. Immunostaining for PARP was more intense in gray and white matter of cases with HIV encephalitis. No clear spatial relationship existed between expression of DNA repair enzymes and the spatial proximity of microglial nodules or HIV-infected macrophages. The cytoplasm of cortical and subcortical neurons immunostained for APP Stronger cortical neuronal APP staining was observed in cases without HIV encephalitis. Staining of deep gray matter neurons was similar, irrespective of the presence or absence of encephalitis. While foci of intense APP staining were noted in white matter not related to HIV infection, they were associated with foci of opportunistic infections (e.g. due to CMV or PML). We conclude that damaged DNA and altered patterns of expression of DNA repair proteins and APP are common findings in the brains of AIDS patients at autopsy, but do not have a spatial relationship to HIV-infected macrophages.

AIDS Dementia Complex↗

Piggybacking intraocular implants to correct pseudophakic refractive error.

OBJECTIVE: To determine the safety and efficacy of implanting a second intraocular lens (IOL) to correct pseudophakic refractive error. DESIGN: Noncomparative, prospective, consecutive case series. PARTICIPANTS: Eight eyes of eight normal pseudophakes and seven eyes of seven postpenetrating keratoplasty (PK) pseudophakes were included in the study. INTERVENTION: A second intraocular lens (IOL) was implanted anterior to the first in each eye in the study. MAIN OUTCOME MEASURES: Efficacy was determined based on the achieved refractive correction and Snellen uncorrected visual acuity measurements. Safety was determined based on loss of best-corrected visual acuity and operative and postoperative complications. RESULTS: Before surgery, spherical equivalents ranged from -5.12 diopters (D) to 7.5 D, with a mean absolute deviation from emmetropia of 3.38 D (1.62). After surgery, spherical equivalents ranged from -2.75 D to 0.5 D, with a mean absolute deviation from emmetropia of 1.21 D (0.90). Before surgery, only 7% of patients had 20/40 or better uncorrected vision, whereas after surgery, 50% had that level of vision. CONCLUSIONS: Implanting a second IOL is a viable option for correcting pseudophakic refractive error.

Humans↗

Combined cataract and glaucoma surgery: trabeculectomy versus endoscopic laser cycloablation.

PURPOSE: To determine whether combined cataract surgery with endoscopic laser cycloablation produces less inflammation than cataract surgery combined with a filtering procedure. SETTING: Taylor Regional Hospital (surgeries) and EyeSight Associates (examinations), Warner Robins, Georgia, USA. METHODS: A randomized prospective study was conducted of 58 eyes of 58 patients comparing endoscopic laser cycloablation performed through a cataract incision at the time of cataract surgery with combined trabeculectomy and cataract surgery. RESULTS: Mean follow-up was 2 years. At the final available visit, 30% of endoscopic laser patients achieved intraocular pressure control (below 19 mm Hg) without medication and 65% with medication. Forty percent of trabeculectomy patients achieved control without medication and 52% with medication. Four endoscopic laser patients (14%) and 3 trabeculectomy patients (10%) were considered treatment failures (required additional surgical intervention). CONCLUSION: Endoscopic laser cycloablation performed through a cataract incision was a reasonably safe and effective alternative to combined cataract and trabeculectomy surgery, providing an option for cataract patients who have glaucoma requiring surgical intervention.

Cataract↗

Nonradioactive Northern blotting with biotinylated and digoxigenin-labeled RNA probes.

The application of nonradioactive RNA probes for Northern blotting offers the advantage of a rapid turn-around time for results without the loss of sensitivity for target mRNA detection. However, a problem that has impeded the widespread use of nonradioactive RNA probes for use in Northern blotting is the difficulty in stripping these probes from nylon membranes after hybridization. In this report we describe two protocols for stripping digoxigenin (Dig)-labeled RNA probes from nylon membranes. One protocol utilizes a phosphate-buffered formamide stripping solution to remove nonchemically modified (regular) RNA probes while the other method utilizes strippable probes that were produced with a chemically modified nucleotide (CTP) and removed by a specific stripping solution. This latter method was developed by Ambion Inc. and is called Strip-EZ. We also describe a protocol for the detection of two separate rat mRNAs using both biotin and digoxigenin-labeled RNA probes that does not require stripping the membrane after hybridization. Finally, we describe the use of another new labeling technology, called Chem-Link, that quickly and conveniently labels RNA for use in Northern blotting.

Animals↗

Production of digoxigenin-labelled RNA probes and the detection of cytokine mRNA in rat spleen and brain by in situ hybridization.

Non-radioactive in situ hybridization is a sensitive method for determining the site of production for secretory molecules such as cytokines. We report here on the central and peripheral induction of proinflammatory cytokines by endotoxin, and outline procedures for the generation and application of rat-specific digoxigenin (Dig)-labelled RNA probes for the localization of mRNA by in situ hybridization. Rats were injected either intravenously (i.v.) or intracerebroventricularly (i.c.v.) with vehicle or lipopolysaccharide (LPS) and sacrificed at various time intervals post-injection. Rats were then perfused with 4% paraformaldehyde and the spleens and brains were removed and cryoprotected in 30% sucrose. Dig-labelled, rat-specific, antisense and sense RNA probes were generated by in vitro transcription from PCR-derived templates. Positive staining with all the antisense probes was cytoplasmic, whereas the sense probes showed no staining. Numerous tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) mRNA positive cells were observed in the marginal zone and in the red pulp of the spleen after iv LPS injections, whereas sections from saline-treated animals showed minimal cytokine mRNA expression. Cells positive for TNF-alpha and IL-1beta mRNA were detectable in the brain after i.c.v. injections of LPS, but not after icv injection of vehicle. An antisense probe for c-fos was utilized in these studies as a positive control for our procedure due to its anatomically specific expression in the rat brain after LPS. In conclusion we have demonstrated that in situ hybridization with Dig-labelled RNA probes is an efficient, sensitive and reliable tool to localize cytokine mRNA production in rat tissue.

Actins↗

Multiple sclerosis: altered expression of 70- and 27-kDa heat shock proteins in lesions and myelin.

Recent studies have implicated heat shock proteins (HSP) in the pathogenesis of the multiple sclerosis (MS) lesion. Expression of the 73 kDa constitutive HSP (HSC70), the 72 kDa stress-inducible HSP (HSP70), and the 27 kDa small HSP (HSP27) was analyzed in white matter and myelin from central nervous system (CNS) tissue of MS and normal subjects using a combination of immunocytochemistry and quantitative immunoblotting. Plaques of all types were sharply defined by reduced immunostaining for HSC70, and shown by immunoblotting to contain 30 to 50% less HSC70 than surrounding white matter or normal tissue. In contrast, HSP27 was markedly enhanced 2.5- to 4-fold in plaque regions, especially in fibrous astrocytes and in hyperplastic interfascicular oligodendrocytes at the lesion edge. HSP70 was less abundant than HSC70, and no significant differences in HSP70 levels were noted between MS and normal white matter. Myelin isolated from active plaques contained 3- to 4-fold more HSC70 than normal myelin. Pronounced expression of HSP70 and HSP27 was also found in MS myelin, although neither protein was detected in normal myelin. Thus, white matter undergoing immune-mediated destruction in MS was associated with altered distribution and expression of HSC70 and HSP27. These changes may initially serve to protect myelin from further destruction and facilitate repair; however, enhanced expression of HSC70, HSP70, and HSP27 in myelin may subsequently present as additional immune targets involved in the progression of disease.

Astrocytes↗

Combined cataract and glaucoma procedures using temporal cataract surgery.

PURPOSE: To evaluate whether separating the procedures in a combined procedure by performing a temporal cataract incision and superior trabeculectomy induces the lower astigmatism of a temporal cataract incision without sacrificing intraocular pressure (IOP) control. SETTING: EyeSight Associates, Warner Robins, Georgia. METHODS: This study evaluated 50 consecutive eyes receiving a superior cataract incision with a superonasal trabeculectomy and 65 eyes receiving a temporal cataract incision with a superonasal trabeculectomy. RESULTS: After 3 months, a substantially greater proportion of temporal incision cases had controlled IOP without medication. A substantially higher proportion in the superior incision group had uncontrolled IOP at each time period. Mean surgically induced cylinder was higher in the superior incision group at every time period. The superior group had early with-the-rule mean induced cylinder that decayed to against-the-rule, with a mean induced cylinder with keratometry at the final available visit (more than 3 months) of -1.01 diopter (D). The temporal group started with a negligible induced cylinder (-0.13 D) that drifted slightly with the rule to a final mean induced cylinder of +0.49 D. At the last visit, 31% in the superior incision group and 57% in the temporal incision group had an uncorrected visual acuity of 20/40 or better, and 72% and 94%, respectively, had a best corrected acuity of 20/40 or better. CONCLUSION: Separating the cataract and glaucoma procedures frees the surgeon to use newer astigmatically neutral techniques for the cataract incision.

Aged↗

Karyotyping of at risk fetuses by cordocentesis in advanced gestation.

Fetal blood obtained by cordocentesis was cultured to obtain rapid karyotypes of fetuses at risk during the late second trimester. Ninety nine fetal blood samples were studied for chromosomal abnormalities. The commonest indications for the procedure were abnormalities detected on ultrasonography (47.7%), and previous child with Down syndrome. Analysis of the 67 successful cultures showed four (5.9%) karyotypic abnormalities. The technique proved helpful in the obstetrical management of at risk fetuses.

Adult↗

A clinical and cytogenetic study of Turner syndrome.

Forty five case of Turner syndrome diagnosed in the Genetics Clinic, between January 1986 and December 1993, were analyzed. The most commonly observed karyotype was 45, X (44.4%), followed by 45, X/46, XX mosaicism (24.4%). Less frequently demonstrated karyotypes were 45, X/46, X, i (Xq) mosaicism and 46, X, i (Xq) (13.3%). Mosaicism for chromosome was seen in 6.7% of patients. Patients with 45, X karyotype had short stature (85%), dysmorphic facies (60%), delayed appearance of secondary sexual characters (100%) and primary amennorhea (100%). Those with 45, X/46, XX mosaicism were less often dysmorphic and presented with either primary or secondary amenorrhea. Patients with 45, X karyotype were younger at diagnosis and had a significantly shorter mean adult height than those with 45, X/46, XX mosaicism. The phenotype in patients with other karyotypic abnormalities was similar to the 45, X group. Short stature and primary or secondary amenorrhea occurring together in a female strongly suggests the possibility of Turner syndrome, which should be confirmed by chromosomal analysis.

Adolescent↗

The effects of kainic acid-induced lesions in the lateral septal area on cell-mediated immune function.

The lateral septal area (LSA) is a primary control region for psychoneuroendocrine functions, and we have previously reported that kainic acid (KA) lesions in the LSA and the hippocampus have inhibitory and facilitatory effects, respectively, on the humoral immune response of female rats. Thus, these limbic structures may selectively participate in directing neuroimmune regulation. In order to assess the fundamental role of the LSA in neuroimmune regulation, we have evaluated the effects of neurotoxic septal lesions on various cell-mediated immune measures. Animals received stereotaxically guided bilateral infusions of KA (2.0 micrograms/microliter) or physiological saline (SHAM) into the LSA. Following a 2-week recovery period, animals were sacrificed and the spleen cells analyzed for natural killer (NK) cell activity and T-cell responsiveness to mitogen (ConA) or to anti T-cell receptor mAb (R73). A separate group of LSA-lesioned animals were immunized with sheep red blood cells 4 days prior to harvesting the spleen for plaque forming cell (PFC) number determination and measurement of TNF-alpha secretion from splenic macrophages. The results indicate that rats with KA lesions in the LSA have significantly higher NK cell activity, significantly lower numbers of splenic PFCs, and significantly reduced TNF-alpha secretion from splenic macrophages, relative to controls. There was a statistical tendency (p < .1) for reduced T-cell lymphoproliferative responses to ConA stimulation in LSA-lesioned animals, relative to SHAMs. However, the T-cell lymphoproliferative response to specific activation via the T-cell receptor was not significantly different between lesioned and control groups. These results further demonstrate the importance of KA-sensitive LSA neurons in neuroimmunoregulation. Moreover, selective alterations of different components of the immune system are observed in LSA-lesioned animals, suggesting that the LSA is involved in the complex and differential regulation of immunity.

Animals↗

On classification of post-mortem multiple sclerosis plaques for neuroscientists.

Plaque classification is proposed based on observation of 348 plaques from 52 post-mortem multiple sclerosis (MS) cases. Four plaque types, ranging from 'earliest lesion' to 'inactive', are described according to immunological activation and degree of demyelination, seen by expression of the Major Histocompatibility Complex (MHC) Class II molecule, HLA-DR, and by Oil Red O staining, respectively. 40% of the plaques were inactive. This result highlights the need for a description of plaque activity for studies of the etiopathogenesis of MS; that is, the earliest and/or the most active plaques should contain the causative agent whereas the burnt out plaques should not.

Adult↗

Reversal of Vinca alkaloid resistance by anti-P-glycoprotein monoclonal antibody HYB-241 in a human tumor xenograft.

A panel of monoclonal antibodies (MAbs) to P-glycoprotein was developed by immunization of mice with multidrug-resistant human neuroepithelioma and neuroblastoma cells. All the anti-P-glycoprotein MAbs reacted with the extracellular portion of P-glycoprotein. The MAbs were examined for their ability to enhance accumulation of actinomycin D, vincristine, vinblastine, and doxorubicin in the human mdr1 transfectant cell line, BRO/pFRmdr1.6. HYB-241, an IgG1 anti-P-glycoprotein MAb, was the most effective modulator, increasing actinomycin D levels in the transfectant line by 6-fold, vincristine by 2-fold, and vinblastine levels by 3-fold. None of the MAbs were capable of modifying the accumulation of doxorubicin. HYB-241 lowered the 50% inhibitory concentration values of actinomycin D by 11-fold, vincristine by 6-fold, and vinblastine by 2-fold. No effect on the 50% inhibitory concentration values of doxorubicin or gramicidin were seen. 111In-labeled HYB-241 localized in human tumor xenografts of BRO/pFRmdr1.6 in nude mice (25% injected dose/g at 120 h). Mice with established drug-resistant xenografts were treated with antibody 24 h prior to the injection of Vinca alkaloid at concentrations known to be non-growth inhibitory. The addition of HYB-241 at 25 mg/kg per injection prior to drug resulted in a significant inhibition of growth of this drug-resistant tumor.

ATP Binding Cassette Transporter, Subfamily B, Mem↗