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Biomedical subjects

S Fisher

Publications and source records attributed to S Fisher.

At least 19 recordsLinked to original sources
PubMed2006

Exserohilum: an emerging human pathogen.

Exserohilum is a dematiaceous fungus that may cause a spectrum of diseases in humans, including skin and corneal infection, invasive disease, and allergic fungal sinusitis. The aim of this work is to describe two new cases of Exserohilum infection and to review the literature. The review yielded 33 cases of Exserohilum infection, of which 23 were reported since 1993. Most occurred in regions with hot climates, such as India, Israel, and the southern USA. Impaired immunity was present in the majority of patients with invasive and skin infections, whereas local trauma and atopy were the predisposing factors in those with corneal infections and allergic fungal sinusitis, respectively. Surgical debridement was the principal mode of therapy for allergic fungal sinusitis. Amphotericin B was the initial single antifungal agent used in all cases of invasive disease; the response rate was low but improved with the addition of triazole agents. Outcome appeared to be better than for other mold infections and depended mainly on the underlying diseases.

Adolescent↗
PubMed2006

Natriuretic peptide and adrenomedullin levels in chronic renal failure and effects of peritoneal dialysis.

Plasma levels of B-type natriuretic peptide (BNP) and its N-terminal propeptide (NT-BNP) are elevated in renal impairment and provide a robust prognostic index. The effect of peritoneal dialysis on plasma NT-BNP, however, is unknown. Furthermore, no information exists regarding levels of the N-terminal propeptide for C-type natriuretic peptide (NT-CNP) in renal failure and the effects of peritoneal dialysis. Accordingly, we documented venous levels of these peptides, and adrenomedullin, across peritoneal dialysis. We measured venous BNP, NT-BNP, NT-CNP, adrenomedullin, blood urea nitrogen (BUN) and creatinine before, during and after completion of overnight peritoneal dialysis in 11 patients, and identical sampling was carried out in eight patients (controls) but between peritoneal dialysis treatments. Peptide levels were measured using well-validated, published methods. Baseline levels of NT-CNP (212, 150-303 pmol/l, median and 25th and 75th percentiles) were much higher than recorded previously in healthy volunteers or in heart failure, and correlated with plasma creatinine (rs=0.53, P<0.05). Peritoneal dialysis had no effect on plasma NT-CNP, nor on NT-BNP, BNP or adrenomedullin (all elevated above normal), whereas both BUN and creatinine levels, as expected, declined (P<0.001). We conclude that plasma levels of NT-CNP are grossly elevated in chronic renal failure and correlated with plasma creatinine, but are not altered by peritoneal dialysis. Likewise, BNP, NT-BNP and adrenomedullin are elevated but are not altered by peritoneal dialysis. This information is needed if levels of these hormones are to be used as prognostic indicators or as a guide to the management of patients with chronic renal failure.

Adrenomedullin↗
PubMed2005

Deep Impact: observations from a worldwide Earth-based campaign.

On 4 July 2005, many observatories around the world and in space observed the collision of Deep Impact with comet 9P/Tempel 1 or its aftermath. This was an unprecedented coordinated observational campaign. These data show that (i) there was new material after impact that was compositionally different from that seen before impact; (ii) the ratio of dust mass to gas mass in the ejecta was much larger than before impact; (iii) the new activity did not last more than a few days, and by 9 July the comet's behavior was indistinguishable from its pre-impact behavior; and (iv) there were interesting transient phenomena that may be correlated with cratering physics.

Cosmic Dust↗
PubMed2005

Possible genotype-phenotype correlations in children with mild clinical course of Canavan disease.

Canavan disease is characterised as a rare, neurodegenerative disease that usually causes death in early childhood. It is an autosomal recessive disorder due to an aspartoacylase (ASPA) deficiency. The causative gene has been mapped to chromosome 17 pter-p13. Here we describe three affected children from two Greek families with an unusually mild course of Canavan disease. All children presented with muscular hypotonia and macrocephaly. Diagnosis was based on elevated N-acetylaspartate in urine, reduced aspartoacylase activity in fibroblasts, and marked white matter changes on cerebral imaging. All three affected individuals exhibited continuous psychomotor development without any regression. Genetic analyses revealed compound heterozygous mutations (Y288 C; F295 S) in two individuals. The Y288 C variant was previously described in a child with macrocephaly, mild developmental delay, increased signal intensity in the basal ganglia, partial cortical blindness and retinitis pigmentosa, and slightly elevated N-acetylaspartate in the urine. Demonstration of the same variant in two unusually mildly affected Canavan disease patients and absence of this variant in 154 control chromosomes suggest a possible pathogenic role in mild Canavan disease. In the third individual, two homozygous sequence variants were identified, which comprise the known G274R mutation and a novel K213E variant.

Adolescent↗
PubMed2004

Refining the Amsterdam Criteria and Bethesda Guidelines: testing algorithms for the prediction of mismatch repair mutation status in the familial cancer clinic.

PURPOSE: Hereditary nonpolyposis colon cancer (HNPCC) is a Mendelian dominant syndrome of bowel, endometrial, and other cancers and results from germline mutations in mismatch repair (MMR) genes. HNPCC is now best diagnosed on molecular grounds using MMR mutation screening, aided by microsatellite instability (MSI) and immunohistochemistry in tumors. Selection of families for molecular investigation of HNPCC is usually based on suboptimal methods (Amsterdam Criteria or Bethesda Guidelines), but these can be improved using additional clinical data (mean ages of affected persons and presence of endometrial cancer) in a quantitative model. METHODS: We have verified the performance of the Wijnen model and have shown that it remains valid when HNPCC is diagnosed using mutation screening, MSI, and immunohistochemistry. We have also set up and verified our own models (Amsterdam-plus and Alternative), which perform at least as well as the Wijnen model. RESULTS: The Amsterdam-plus model improves on the Amsterdam Criteria by using five extra variables (numbers of colorectal and endometrial cancers in the family, number of patients with five or more adenomas, number with more than one primary cancer of the colorectum or endometrium, and mean age of presentation) and performs better than the Wijnen model. The Alternative model avoids the need to evaluate the Amsterdam Criteria and performs nearly as well as the other models. CONCLUSION: We believe that a quantitative model, such as the Amsterdam-plus model, should be the first choice for selecting families or patients for evaluation of HNPCC using molecular tests. We present an algorithm for this process.

Adult↗
PubMed2004

Postpartum cerebral angiopathy: atypical features and treatment with intracranial balloon angioplasty.

Postpartum cerebral angiopathy (PCA) is an uncommon cause of ischemic and hemorrhagic stroke in young women. It is usually clinically benign and not relapsing. We describe a patient with nonhemorrhagic PCA who had an atypical progressive neurological deficit from bilateral hemisphere watershed ischemia despite treatment with aggressive medical therapy and intracranial balloon angioplasty.

Adult↗
PubMed2004

Falling estradiol levels as a result of intentional reduction in gonadotrophin dose are not associated with poor IVF outcomes, whereas spontaneously falling estradiol levels result in low clinical pregnancy rates.

BACKGROUND: Although estradiol levels remain an integral part of monitoring in most IVF programmes, the effect of falling estradiol on IVF outcome has not been adequately quantified. The objective of this study was to evaluate the effect of falling estradiol levels prior to hCG on IVF outcome. METHODS: This was a retrospective cohort study carried out in a university-based fertility clinic. A total of 112 IVF patients in whom estradiol levels fell prior to the administration of hCG were matched for age and year of treatment with 112 control IVF patients. IVF outcomes including oocytes retrieved, fertilization rate, embryos for transfer, and pregnancy rates were compared between the groups. RESULTS: Seventy per cent of women in the falling estradiol group experienced spontaneously falling estradiol levels. Spontaneously falling estradiol was associated with fewer oocytes retrieved (median 5 versus 8, P=0.001), increased rates of failed fertilization (18 versus 6%, P=0.018) and lower clinical pregnancy rates (12 versus 26%, P=0.012) compared to controls. Despite marked decreases in estradiol levels, IVF outcomes for patients whose estradiol levels fell as a result of deliberate protocol modification had similar fertilization and clinical pregnancy rates as controls. CONCLUSIONS: Subtle (<10%) spontaneous decreases in estradiol levels are associated with very poor IVF outcomes.

Adult↗
PubMed2004

Comparison of selected analytical techniques for protein sizing, quantitation and molecular weight determination.

Protein analysis techniques are developing fast due to the growing number of proteins obtained by recombinant DNA techniques. In the present paper we compare selected techniques, which are used for protein sizing, quantitation and molecular weight determination: sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), lab-on-a-chip or microfluidics technology (LoaC), size exclusion chromatography (SEC) and mass spectrometry (MS). We compare advantages and limitations of each technique in respect to different application areas, analysis time, protein sizing and quantitation performance.

Chromatography↗
PubMed2002

The addition of antiemetics to the morphine solution in patient controlled analgesia syringes used by children after an appendicectomy does not reduce the incidence of postoperative nausea and vomiting.

BACKGROUND: We studied the effect of intraoperative ondansetron 0.1 mg x kg(-1) or droperidol 0.01 mg.kg-1, followed by the same dose of the antiemetic agent added to the morphine solution during patient controlled analgesia (PCA) on the incidence of nausea and vomiting in children following an appendicectomy. METHODS: Sixty children, aged 5-13 years, were recruited and randomly allocated to receive no prophylactic antiemetic, the control group (group C), ondansetron (group O) or droperidol (group D). The PCA pump was programmed to deliver a bolus dose of 20 microg x kg(-1) of morphine.with a 5-min lockout period and a background infusion of 4 microg x kg(-1) x h(-1). RESULTS: Postoperatively, the three groups were compared for nausea, vomiting and sedation scores for 24 h. The incidence of postoperative nausea and vomiting was 33% for group C, 44% for group O and 41% for group D. There was no increase in sedation scores in the droperidol group. CONCLUSIONS: We were unable to show any significant benefit from the prophylactic administration of ondansetron or droperidol to children using morphine PCA devices following appendicectomy in the doses we employed.

Analgesia, Patient-Controlled↗
PubMed2001

Nucleotide sequence analysis of varicella-zoster virus glycoprotein E epitope coding regions.

Varicella-zoster virus (VZV) glycoprotein E [gE] contains 623 amino acid residues. Fifty percent of the gE gene, codons 39 to 344 that encompasses two epitope coding regions e1 and c1, was sequenced and analyzed for variation among the 30 VZV isolates. A total of eleven isolates showed variance when compared with Dumas VZV strain sequence through base substitutions, with two isolates showing an amino acid change of tryptophan to arginine outside the coding regions of the epitopes e1 and c1 that are recognized by monoclonal antibodies 4F9 and c1, respectively. The results suggest that these epitopes were stable in the various VZV isolates. Thus, VZV glycoproteins with conserved epitopes are suitable candidates for both primary and booster vaccines.

Adult↗
PubMed2001

Near haploid childhood acute lymphoblastic leukemia masked by hyperdiploid line: detection by fluorescence in situ hybridization.

Near-haploid (<30 chromosomes) acute lymphoblastic leukemia (ALL) is a rare and unique subgroup of childhood common ALL associated with a very poor outcome. It may be underdiagnosed when masked by a co-existing hyperdiploid line, which has to be distinguished from the common good-prognostic hyperdiploid (>50 chromosomes) ALL. We present three children in whom, by conventional cytogenetics, near-haploid ALL was detected on relapse. Using interphase FISH probes of chromosomes X, Y, 4, 12, and 21, we were able, in two cases, to trace the hidden near-haploid lines of approximately 5% and 20% of the cells, masked by hyperdiploid cells of approximately 80% and 70%, respectively; at relapse, the proportion was reversed, with predominant near-haploid lines of over 80% and residual hyperdiploidy of less than 10%. The near-haploid lines consisted of 24 and 27 chromosomes, and always retained the second copy of chromosome 21 or its derivative, as detected in one of our patients by SKY. The hyperdiploid clones were the exact duplicates of the near-haploid ones and contained four and two copies of the chromosomes represented in two and one copies in the near-haploid stem line, respectively. Unlike the common hyperdiploid ALL, no trisomies were observed. The patients were all aged >10 years, with WBC 0.7-30 x 10(9)/L, and a common ALL phenotype. They were treated with the ALL-BFM-95 protocol, medium risk group, and responded well to 8 days of steroid therapy, but relapsed early, within 11 months, and died a few months later. Interphase FISH technique is recommended for the detection of cryptic near-haploid clones in the diagnostic survey of ALL. To assess the prognostic value of near-haploidy in the context of the ALL-BFM protocols, a larger cohort of patients is required.

Adolescent↗
PubMed2001

Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations.

Background Genetic predisposition to inflammatory bowel disease (IBD) has been shown by epidemiological and linkage studies. Genetic linkage of IBD to chromosome 16 has been previously observed and replicated in independent populations. The recently identified NOD2 gene is a good positional and functional candidate gene since it is located in the region of linkage on chromosome 16q12, and activates nuclear factor (NF) kappaB in response to bacterial lipopolysaccharides. Methods We sequenced the coding region of the NOD2 gene and genotyped an insertion polymorphism affecting the leucine-rich region of the protein product in 512 individuals with IBD from 309 German or British families, 369 German trios (ie, German patients with sporadic IBD and their unaffected parents), and 272 normal controls. We then tested for association with Crohn's disease and ulcerative colitis. Findings Family-based association analyses were consistently positive in 95 British and 99 German affected sibling pairs with Crohn's disease (combined p<0.0001); the association was confirmed in the 304 German trios with Crohn's disease. No association was seen in the 115 sibling pairs and 65 trios with ulcerative colitis. The genotype-specific disease risks conferred by heterozygous and homozygous mutant genotypes were 2.6 (95% CI 1.5-4.5) and 42.1 (4.3-infinity), respectively. Interpretation The insertion mutation in the NOD2 gene confers a substantially increased susceptibility to Crohn's disease but not to ulcerative colitis.

Alleles↗
PubMed2001

Inhibitors of the bacterial cell wall biosynthesis enzyme MurC.

A series of phosphinate transition-state analogues of the L-alanine adding enzyme (MurC) of bacterial peptidoglycan biosynthesis was prepared and tested as inhibitors of the Escherichia coli enzyme. Compound 4 was identified as a potent inhibitor of MurC from Escherichia coli with an IC(50) of 49nM.

Cell Wall↗
PubMed2001

Apoptosis: one of the mechanisms that maintains unresponsiveness of the intestinal mucosal immune system.

Intestinal mucosa is constantly exposed to environmental AGS: Activation of lamina propria (LP) T cells by luminal Ags may lead to the production of inflammatory cytokines and subsequent mucosal inflammation and tissue damage. However, in normal circumstances, LP T cells do not respond to antigenic stimulation. The mechanisms of this unresponsiveness in healthy subjects are not fully understood. In this study, we found by in vivo analysis that, except for T cells in lymph nodules of the mucosa, 15% of LP T cells underwent apoptosis in normal individuals. In contrast, there was a marked reduction in apoptosis of LP T cells in patients with inflammatory bowel disease (Crohn's disease and ulcerative colitis) and those with specific colitis. Our findings suggest that apoptosis might be a mechanism that turns off mucosal T cell responses to environmental Ags in healthy subjects, and resistance to apoptosis could be an important cause of mucosal immune dysregulation and tissue inflammation in colitis.

Apoptosis↗
PubMed2001

Tumor progression despite efficient tumor antigen cross-presentation and effective "arming" of tumor antigen-specific CTL.

To determine whether APC function or "arming" of CTL for lytic function are the points at which Ags from a nonimmunogenic tumor fail to induce an effective immune response, we established a murine tumor model that expressed intracellular OVA and selected a clone (cOVA-9) that remained susceptible to lysis by specific CD8(+) T cells throughout tumor growth. Viable cOVA-9 tumor cells grew in normal mice at a rate similar to the parental tumor, and vaccination with irradiated cOVA-9 cells did not induce protection against itself or the parental line, confirming its nonimmunogenic status. In vivo evaluation during tumor growth demonstrated persisting tumor Ag cross-presentation accompanied by the generation of potent, specific CTL which were detectable when tumors were barely palpable. Despite the presence of highly active CTL in the tumor-draining lymph nodes, there was no apparent lysis of tumor-associated APC. These data show that tumor-draining APC are not dysfunctional with regard to two crucial processes, in vivo tumor Ag cross-presentation and specific CTL arming, and that failure to prevent tumor growth is not in the induction phase, but in the effector phase and occurs within the tumor itself before the tumor matrix is established.

Animals↗
PubMed2001

Physician intervention and patient risk perception among smokers with acute respiratory illness in the emergency department.

BACKGROUND: Acute Respiratory Illness accounts for over 12 million visits to emergency departments in the United States each year. Between one-fourth and one-half of these patients are smokers. We examined the frequency of physician intervention for smoking cessation among acute respiratory illness patients in the emergency department, and examined the influence of physician intervention on patients' perceived risk from smoking and motivation to quit. METHODS: This study was conducted in the emergency department of a large inner-city hospital. Adult smokers (n = 63) presenting with symptoms of acute respiratory illness were surveyed by exit interview while in the emergency department. The frequency and extent of physician interventions for smoking were examined using the Agency for Health Care Policy and Research guidelines as a model. We also assessed patients' perceptions of risk from smoking, the presence of other household smokers, and the patients' motivation to quit. RESULTS: Emergency department physicians provided incomplete and inconsistent intervention for smoking. While most patients reported being asked if they smoked, only half of smokers were advised to quit. Only 9% were offered any assistance with quitting. Risk perception was generally low, however, the majority of smokers were willing to receive on-site smoking cessation counseling while in the emergency department. CONCLUSIONS: The small sample size in this study requires that results be interpreted with caution. However, the findings of this study suggest that the emergency department setting may provide a unique "teachable moment" in which to initiate smoking cessation counseling for this high-risk population.

Adolescent↗