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Biomedical subjects

S Alexander

Publications and source records attributed to S Alexander.

At least 19 recordsLinked to original sources
PubMed2006

Cyanoacrylate in the treatment of gastric varices complicated by multiple pulmonary emboli.

Bleeding gastric varices are increasingly being obliterated with the aid of endoscopic injection of n-butyl-cyanoacrylate (histoacryl) diluted with lipiodol. This glue acts as a tissue adhesive that polymerizes on contact with blood in a gastric varix. Severe glue pulmonary embolism is a rare complication of injection therapy. This case involves a 52-year-old man with fundal gastric varices, who developed multiple pulmonary emboli following glue injection with profound hypoxia requiring hospital admission for 13 days, but with eventual recovery of normal lung function.

Contrast Media↗
PubMed2006

The prevalence of proline iminopeptidase negative Neisseria gonorrhoeae throughout England and Wales.

BACKGROUND: The accurate laboratory identification of Neisseria gonorrhoeae is an essential element of the diagnosis of gonorrhoea and is particularly important for medicolegal cases. The detection of proline iminopeptidase (Pip) activity is widely used as a marker for gonococci, although Pip negative N gonorrhoeae isolates have been shown to generate false negative identifications when using biochemical kits. This study aimed to determine the frequency of Pip negative gonococci in England and Wales. METHODS: A total of 2055 isolates were collected from consecutive patients attending 26 genitourinary medicine centres as part of the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP). Upon receipt the identity of all isolates was confirmed using N gonorrhoeae specific monoclonal antibodies and the Pip status was determined using the Gonochek II kit. RESULTS: The overall prevalence of Pip negative isolates was found to be 4.33%. Significant geographical variation was observed between isolates from centres outside London (p< or =0.001). Variation was also observed within London between the nine different clinics submitting isolates (p = 0.025). There was also a higher frequency of these isolates among men who have sex with men (p< or =0.001), which may account for geographical variations. CONCLUSION: Pip negative N gonorrhoeae isolates are a very serious cause for concern as currently all biochemical test kits available within the United Kingdom require the presence of the Pip enzyme for an unambiguous identification of this pathogen. Raising awareness of the current prevalence of Pip negative N gonorrhoeae isolates is critical for the successful control of gonorrhoea.

Aminopeptidases↗
PubMed2005

Alpha7-acetylcholine receptor antibodies in two patients with Rasmussen encephalitis.

Rasmussen encephalitis (RE) sera were screened for antibodies to human alpha7 nicotinic acetylcholine receptors (nAChRs) using electrophysiology, calcium imaging, and ligand binding assays. Sera from two of nine patients with RE blocked ACh-induced currents through alpha7 nAChRs and the ACh-induced rise in intracellular free calcium ([Ca2+]i) and inhibited (125)I-alpha-bungarotoxin binding in cells expressing alpha7 nAChRs. Thus, the alpha7 nAChR is a potential target for pathogenic antibodies in patients with RE.

Adolescent↗
PubMed2005

Malignant bone tumors in Kuwait: a 10-year clinicopathological study.

Between 1995 and 2004, 142 malignant bone tumours comprising 76 primary and 66 secondary tumours were identified in the Pathology Department of Al-Sabah Hospital, Kuwait. Pathological fracture was the presenting sign in 35% of the cases. The mean incidence of primary tumours/year was 3.3 cases/million inhabitants. The primary tumours showed a male predilection and 42% occurred below the age of 20 years. The most frequent in the descending order of frequency were Ewing's sarcoma, multiple myeloma, osteosarcoma, chondrosarcoma and non-Hodgkin's lymphoma. The femur was the most common site for secondary tumours; more than half of the tumours with metastases at this site originated in the breast. The high frequency of Ewing's sarcoma is noteworthy and requires further investigation.

Adolescent↗
PubMed2005

env Gene typing of human immunodeficiency virus type 1 strains on electronic microarrays.

The NanoChip system was used for subtyping human immunodeficiency virus type 1 (HIV-1) strains using probes complementary to the V1 region of the env gene. Probes for six subtypes (A to D, F, and G) and two circulating recombinant forms (AG and AE) of HIV-1 group M were included. The specificity of these oligonucleotides had been evaluated previously in a DNA enzyme immunoassay. Samples from 112 patient sera were used as templates in a nested reverse transcription-PCR to produce amplicons that were applied to the array. The array was then hybridized successively to pairs of oligonucleotide probes. The strains were assigned a subtype on the basis of their probe hybridization patterns. One strain gave a contradictory pattern and was designated as untypeable by the NanoChip assay. Eighty-eight strains gave hybridization patterns that allowed a correct subtype designation to be made by the NanoChip assay compared to either the sequence or the heteroduplex mobility assay (HMA)-determined subtypes. Thirteen strains that reacted with the subtype A probe (SA2) were incorrectly assigned to subtype A, or to one of the related circulating recombinant types (AE or AG), on the basis of reactions with probe SAE1 or SAG1. The results indicate that these oligonucleotides have relatively low specificities. The probe subtypes of three strains matched the subtypes determined for the gag and pol genes but not the env gene, suggesting that a recombination event may have occurred within the env gene. Overall, the NanoChip assay gave results comparable to those for HMA and sequencing and provides a convenient and cost-effective means by which to subtype HIV-1.

Electronics↗
PubMed2004

[Mode of delivery and term breech presentation in the PREMODA cohort].

OBJECTIVES: The purpose of this work was to report labor and birth management practices for term breech presentation in France and Belgium in 2001-2002 and to describe indications for cesarean sections (before labor, emergency situations) in breech presentations. MATERIAL AND METHODS: The PREMODA cohort is a survey population which included 19408 deliveries, 8108 of which were term breech presentations. RESULTS: Infants were delivered by cesarean section before labor (59.1%), emergency cesarean section during labor (18.4%) or vaginally (22.5%). The decision for cesarean section before labor was empirical (breech presentation) in 44.3% of the cases. Half of the cesarean sections performed during labor (n=704, 49.3%) were planned C-sections. Overall, 67.8% of the breech presentations were delivered during planned cesarean sections (before or during labor). When vaginal delivery was attempted, the rate of vaginal birth was 70%. CONCLUSION: These early results reveal a high rate of cesarean section as well as differences in inter-regional practices. Considering all cesarean sections performed before labor, the most frequent indication was an empirical decision because of the breech presentation. An increased rate of planned cesarean section does not reduce the rate of vaginal delivery when attempted.

Adult↗
PubMed2003

Short-term outcome of isolated and associated congenital heart defects in relation to antenatal ultrasound screening.

OBJECTIVE: To investigate the outcome of fetuses affected by congenital heart defects (CHD), either detected or undetected at ultrasound screening, according to their complexity and severity. DESIGN: The study group comprised 3633 malformed fetuses entered into the Eurofetus database of which 798 had CHD. We compared the short-term outcome in cases where a CHD was detected by ultrasound screening with that in cases where a CHD was not detected. Isolated and associated CHD (ICHD and ACHD) and the degree of severity of defects were considered separately. Outcome data included termination of pregnancy (TOP), intrauterine fetal death, neonatal death (< 6 days after birth), gestational age at diagnosis and at delivery, mode of delivery and birth weight. RESULTS: Of the 798 fetuses with CHD, 595 had ICHD and 203 had ACHD. The diagnosis of an anomaly was made significantly earlier in ACHD cases. TOP was chosen in 28% of cases with a prenatal diagnosis of CHD, 20% for ICHD and 37% for ACHD (P < 0.001). The survival rate of antenatally diagnosed fetuses was lower in those with ACHD than in those with ICHD (P < 0.001) and lower for fetuses with antenatal diagnosis than with postnatal diagnosis (P < 0.001); this was due to significant differences in the complexity and severity of the defect. Premature delivery (< 32 weeks) was more frequent in fetuses in which an antenatal diagnosis of CHD had been made. Severe CHD were diagnosed earlier and were associated with a higher rate of TOP and spontaneous loss. CONCLUSIONS: The severity of CHD has a positive influence on the sensitivity of screening but a negative influence on the outcome. CHD that are not diagnosed antenatally include a high proportion of benign malformations. This explains the apparent paradox of a poorer outcome in fetuses in which a CHD was detected prenatally compared to those fetuses in which the defect was undetected prenatally. However, prenatal diagnosis provides parents with the option of TOP or of preventive care in specialized centers.

Female↗
PubMed2003

Does the use of a specialised paediatric retrieval service result in the loss of vital stabilisation skills among referring hospital staff?

AIMS: To compare the proportion of airway and vascular access procedures performed by referring hospital staff on critically ill children in two discrete time periods, before and after widespread use of a specialised paediatric retrieval service. METHODS: Transport data were obtained from retrieval logs of all children for whom a paediatric retrieval team was launched in each of two time periods (October 1993 to September 1994; and October 2000 to September 2001). RESULTS: The overall intubation rate was similar in the first and second time periods (83.9% v 79.1%). However, 31/51 (61%) retrieved children were intubated by referring hospital staff in 1993-94, compared to 227/269 (84%) in 2000-01. Referring hospital staff gained central venous access in 11% v 18% and arterial access in 22% v 19% of retrieved children in the first and second time periods respectively. This was in spite of a significant reduction in the proportion of children on whom these procedures were performed. CONCLUSION: Referring hospital staff are performing a greater proportion of initial airway and vascular access procedures undertaken in the stabilisation of sick children retrieved by a specialised paediatric retrieval team. The provision of this service has not resulted in the loss of vital skills at the local hospital.

Catheterization↗
PubMed2002

CD80-mediated induction of immunostimulation in two ocular melanoma cell lines is augmented by interferon-gamma.

Although the transfection of the T-cell costimulatory molecule CD80 cDNA into human tumours can augment their immunogenicity in vitro, its expression alone is ineffective in many tumour systems. We evaluated the influence of CD80 expression on the immunostimulatory activity of ocular melanoma cell lines and determined whether IFN-gamma could enhance the effect. Two ocular melanoma cell lines were transfected with CD80 cDNA. The immunostimulatory capacity of the CD80+ transfectants was determined by their ability to stimulate the proliferation of allogeneic peripheral blood mononuclear cells (PBMC). The influence of additional accessory molecules on PBMC proliferation was assessed by pre-treating the CD80 transfectants with IFN-gamma. The CD80+ transfectants induced proliferation of allogeneic PBMC. IFN-gamma treatment of the tumour cells induced upregulated expression of MHC class I, de novo expression of MHC class II and CD54, and enhanced the ability of the CD80+ transfectants to stimulate PBMC proliferation. CD4+ T cells were not required for the proliferative response against untreated CD80+ tumour cells but were necessary for the augmentation of proliferation observed following IFN-gamma treatment. CD80+ ocular melanoma cells possess immunostimulatory potential which is augmented by IFN-gamma induced upregulation of cell surface molecules. Further studies on the role of costimulatory molecules in inducing anti-tumour immunity in ocular melanoma may help to define new strategies for application of immunotherapeutic approaches to treat this aggressive disease.

Antineoplastic Agents↗
PubMed2002

Sensitivity of ultrasound screening for congenital anomalies in unselected pregnancies.

OBJECTIVE: To assess the influence of heart defect frequency and severity on screening sensitivity of the entire spectrum of congenital anomalies (CA) and on detection rate of congenital heart defect (CHD) when performing routine ultrasound screening in unselected pregnant women. STUDY DESIGN: Secondary analysis was performed on data from Eurofetus, a large international collaborative study of ultrasound screening for CA in unselected populations. The present study addressed the relations (i) between the frequency of CHD in the screened population and the global sensitivity of ultrasound in detecting CA; (ii) between frequency of ventricular septum defect (VSD) and detection rate of CA and CHD; and (iii) between seriousness of CHD and CHD sensitivity. RESULTS: A negative correlation (p<0.001) between CHD frequency and CA sensitivity was observed in this study. Likewise, a negative correlation was also found between frequency of VSD and sensitivity for CA or CHD detection (p<0.001). In addition, a positive significant relationship (p<0.001) was observed between sensitivity and severity of CHD. CONCLUSION: A low CHD frequency introduces bias in CA and CHD sensitivity evaluation. Incomplete assessment of fetal and neonatal malformations brings on systematic error, leading to the pre-eminence of severe defects in the studied population sample and artificially improving sensitivity figures. On the other hand, from a clinician's viewpoint, the higher sensitivity for severe defect is welcomed, since their detection is most crucial for appropriate management.

Chi-Square Distribution↗
PubMed2001

Promising early outcomes with a novel, complete steroid avoidance immunosuppression protocol in pediatric renal transplantation.

BACKGROUND: Corticosteroids have been a cornerstone of immunosuppression for four decades despite their adverse side effects. Past attempts at steroid withdrawal in pediatric renal transplantation have had little success. This study tests the hypothesis that a complete steroid-free immunosuppressive protocol avoids steroid dependency for suppression of the immune response with its accompanying risk of acute rejection on steroid withdrawal. METHODS: An open labeled prospective study of complete steroid avoidance immunosuppressive protocol was undertaken in 10 unsensitized pediatric recipients (ages 5-21 years; mean 14.4 years) of first renal allografts. Steroids were substituted with extended daclizumab use, in combination with tacrolimus and mycophenolate mofetil. Protocol biopsies were performed in the steroid-free group at 0, 1, 3, 6, and 12 months posttransplantation. Clinical outcomes were compared to a steroid-based group of 37 matched historical controls. RESULTS: Graft and patient survival was 100% in both groups. Clinical acute rejection was absent in the steroid-free group at a mean follow-up time of 9 months (range 3-13.7 months). Protocol biopsies in the steroid-free group (includes 10 patients at 3 months, 7 at 6 months, and 4 at 12 months) revealed only two instances of mild (Banff 1A) subclinical rejection (reversed by only a nominal increase in immunosuppression) and no chronic rejection. At 6 months the steroid-free group had no hypertension requiring treatment (P=0.003), no hypercholesterolemia (P=0.007), and essentially no body disfigurement (P=0.0001). Serum creatinines, Schwartz GFR, and mean delta height Z scores trended better in the steroid-free group. In the steroid-free group, one patient had cytomegalovirus disease at 1 month and three had easily treated herpes simplex stomatitis, but with no significant increase in bacterial infections or rehospitalizations over the steroid-based group. The steroid-free group was more anemic early posttransplantation (P=0.004), suggesting an early role of steroids in erythrogenesis; erythropoietin use normalized hematocrits by 6 months. CONCLUSIONS: Complete steroid-free immunosuppression is efficacious and safe in this selected group of children with no early clinical acute rejection episodes. This protocol avoids the morbid side effects of steroids without increasing infection, and may play a future critical role in avoiding noncompliance, although optimizing renal function and growth.

Adolescent↗
PubMed2001

Immunohistochemistry of matrix metalloproteinases in reperfusion injury to rat brain: activation of MMP-9 linked to stromelysin-1 and microglia in cell cultures.

Reperfusion damages the blood-brain barrier (BBB). Matrix metalloproteinases (MMPs) are associated with the opening of the BBB, but their cellular localization and activation mechanisms are uncertain. We used immunohistochemistry to determine the cellular localization of the MMPs in reperfused rat brain, and cell cultures to study their activation. Spontaneously hypertensive rats (SHR) had a 90 min middle cerebral artery occlusion (MCAO) followed by reperfusion for times from 3 h to 21 days. Frozen sections were immunostained with antibodies to gelatinase A (MMP-2), stromelysin-1 (MMP-3), and gelatinase B (MMP-9). Sham-operated control rats showed MMP-2 immunostaining in astrocytic processes next to blood vessels. After 3 h of the onset of reperfusion MMP-2 immunostaining increased in astrocytes. At 24 h immunoreactivity for MMP-3 and MMP-9 appeared. MMP-3 co-localized with activated microglia (Ox-42+) and ischemic neurons (NeuN+). MMP-9 immunostaining was seen at 48 h in endothelial cells, neutrophils, and neurons. At 5 and 21 days intense MMP-2 staining was seen in reactive astrocytes around the ischemic core. Studies of activation of the MMP were done in lipopolysaccharide (LPS)-stimulated astrocyte and microglia cultures. Stimulated astrocytes produced an activated form of MMP-2. When microglia were stimulated, they activated MMP-9. Immunostaining showed MMP-3 in cultures of enriched microglial cells. The hydroxymate-type, MMP inhibitor, BB-1101, blocked the activation of MMP-2 and MMP-9 by LPS in mixed glial cultures. We propose that MMP-2 is normally present in astrocytic end feet, and that during ischemia MMP-9 and MMP-3 are produced. MMP-3 in microglia/macrophages may be activating proMMP-9. Our results show that a differential expression of MMPs by astrocytes, microglia, and endothelial cells at the blood vessels is involved in the proteolytic disruption of the BBB.

Animals↗
PubMed2001

Proteomic analysis of a developmentally regulated secretory vesicle.

Secretion of spore coat proteins from the prespore secretory vesicles (PSVs) in Dictyostelium discoideum is a signal mediated event that underlies terminal cell differentiation, and represents an important case of developmentally regulated secretion. In order to study the biochemical mechanisms that govern the regulated fusion of the PSVs with the plasma membrane and the subsequent secretion of their cargo, we purified this organelle from prespore cells. Analysis of protein extracts of highly purified PSVs indicated that, in addition to the cargo of structural spore coat proteins, many more proteins are associated with the PSVs. Their identification is paramount to the understanding of the mechanism of regulated secretion in this system. In this study we have taken the first comprehensive proteomic approach to the analysis of an entire, previously uncharacterized, organelle, with the goal of identifying the major proteins associated with the PSVs. We show that in addition to the structural spore coat proteins, the PSVs contain the enzymes needed for proper spore coat assembly (thioredoxin 2 and 3), regulatory proteins which we predict receive and transduce the developmental signal for secretion (rab7 GTPase, PI-3 kinase, NDP kinase and the calcium binding proteins calfumirin-1 and calreticulin) as well as proteins that interact with the cytoskeleton to mediate movement of the PSVs to the plasma membrane (actin binding proteins coactosin and profilin 1). In addition, the results suggest that proteins can play multiple roles in the cell, and that protein function can be dictated in part by subcellular localization. The identification of the PSV proteins is allowing us to develop testable hypotheses about the roles of these proteins within the functional context of developmentally regulated secretion.

Animals↗
PubMed2001

Transcript mapping and processing of mitochondrial RNA in Dictyostelium discoideum.

The circular mitochondrial genome of Dictyostelium discoideum has a size of 55,564 base pairs. We present here a complete and detailed transcription map of the mitochondrial DNA. Eight major, polycistronic transcripts encoding polypeptides, ribosomal RNAs and interspersed transfer RNAs were identified in Northern hybridization studies. Most of these polycistronic transcripts are subsequently processed into smaller mono-, di- or tricistronic RNAs. In some cases, the maturation involves endonucleolytic cleavage of the transcripts using transfer RNAs as excision signals. Primer extension experiments mapped the 5' ends of the transcripts, which may represent transcription initiation sites. Two of the polycistronic transcripts were found to be overlapping. Based on sequence alignments of the potential transcription start sites, a short oligonucleotide consensus initiation sequence has been identified which does not reveal any significant sequence homologies to known promoter regions from other organisms.

Animals↗
PubMed2001

Filmless in 60 days: the impact of picture archiving and communications systems within a large urban hospital.

Many large urban hospitals converting to filmless radiography use a phased approach for digital imaging implementation. In fact, this strategy often is recommended by picture archival communication systems (PACS) experts and vendors alike for large, busy hospitals installing PACS in existing physical facilities. The concern is that comprehensive conversion from film-based to digital imaging may be too overwhelming an adjustment in operations for a medical staff to effectively handle without serious disruption of workflow for patient treatment and care. Elmhurst Hospital Center is a 543-bed hospital located in the Borough of Queens in New York City. Owned by the New York City Health and Hospitals Corporation, this municipal teaching hospital provides services to a patient mix that is 38% indigent with no insurance, 50% covered by Medicaid or Medicare, and 12% affiliated with HMOs. Most inpatients are admitted through the emergency department. Forty-five percent of all radiology procedures conducted are for emergency patients. Historically, up to 25% of all diagnostic imaging examinations were never reported formally by radiologists. Report turnaround time for the remaining 75% was unacceptable, with only 3% of all imaging examinations reported within a 12-hour period in 1996. Both situations existed in great part because physicians and residents who felt they needed access to films simply took them. Many were never located or returned days after they were taken. In 1998, Elmhurst Hospital Center replaced its RIS and added voice recognition dictation capabilities in January 1999. A hospitalwide PACS was deployed 10 months later. With the exception of mammography, the hospital converted to filmless radiography within 60 days. The critical objectives to maintain control of films and radically improve the reporting process were achieved immediately. Over 99% of all examinations now are formally reviewed and reported. Only 7% of all reports take 1 or more days to generate. This report describes Elmhurst Hospital's efforts to make improvements in the delivery of radiology services and the reasons attributed to its rapid conversion to becoming a filmless (mammography excluded) medical center. The impact of the PACS on radiology department operations and service is discussed.

Hospital Bed Capacity, 500 and over↗
PubMed2001

The pros and cons of implementing PACS and speech recognition systems.

The installation and implementation of a hospitalwide image management system and a speech recognition dictation system has had a dramatic and positive impact on radiology report turnaround times at Elmhurst Hospital Center, a 543-bed municipal teaching hospital located in New York City's Borough of Queens. The "lost film" problem has been eliminated. As a result, the percentage of unreported examinations has dropped from 25% to less than 1%. These performance improvements have significantly benefited the entire medical staff. With the successful implementation of a HL-7 standards-based radiology information system (RIS), a speech recognition dictation system, around-the-clock staffing of Board Certified radiologists, and a picture archiving and communication system (PACS), report turnaround time improved dramatically. Eighty-six percent of all examinations now are reported formally within a 12-hour period compared with a 3% average before implementation of the changes. However, with the use of the PACS and speech recognition technologies, new problems have arisen within the radiology department. These technologies, designed to enhance communications capabilities, also have significantly reduced the amount of clinician/radiologist dialogue. Easy and rapid access to patient images and reports has had a detrimental effect on that face-to-face consultations with clinicians, which were commonplace before PACS, and now have almost completely disappeared. The radiologist/clinician interchanges, which occurred frequently before a final report was dictated, often resulted in better understanding of the clinical problem and, hence, a more meaningful final report. Although a conferencing feature to facilitate communication exists within the PACS, it is not utilized by the clinicians. The dilemma is that as information about patients is made more available to the hospital staff, less information is provided about patients to the radiologists. Although the speech recognition system benefits the hospital, its staff, and the patients served by reducing clinician time awaiting a diagnostic report and reducing clinic and emergency room waiting time by the patients themselves, it does not necessarily benefit the radiologists who use it. Speech recognition dictation systems slow down the individual productivity of the radiologists' dictation process by at least 25%. Radiologists are assuming the role of transcriptionists as well as diagnosticians. Mistakes occur that would not with the use of a traditional dictation system and professional transcriptionists.

Efficiency↗