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Biomedical subjects

S Adams

Publications and source records attributed to S Adams.

At least 37 records · Page 2Linked to original sources
PubMed2001

Magnetic resonance imaging in the diagnosis of Fournier's gangrene.

Magnetic resonance imaging and ultrasound are the imaging modalities recommended in the early diagnosis of Fournier's gangrene. Because of the high mortality of this inflammatory disease early diagnosis is essential to initiate adequate surgical and medical treatment. In the clinical literature only a handful of cases, in which diagnosis of Fournier's gangrene is based on MRI findings, have been reported; therefore, we report another case which shows the ability of MRI especially to determine the point of origin and extension of disease.

Adult↗
PubMed2001

Allogeneic bone marrow transplantation from partially mismatched related donors as therapy for primary induction failure acute myeloid leukemia.

The outcome of acute myeloid leukemia patients with primary refractoriness to conventional chemotherapy is extremely poor. Allogeneic bone marrow transplants with matched sibling or matched unrelated donors provide 10-20% disease-free survival in this setting. We analyzed our transplant experience using readily available partially mismatched related donor (PMRD) in patients with primary induction failure (PIF) AML. Between March 1994 and December 1998, 13 patients with PIF AML were transplanted from 0-3 HLA antigen mismatched donors. All 12 evaluable patients engrafted at a median of day +16. Ten (77%) patients survived at least 100 days after transplant. Acute GVHD (grade II) was observed in one of 12 patients. Chronic GVHD was seen in one of 10 patients surviving beyond day 100. The major cause of failure was relapse of disease in six occurring 3-12 months after PMRD BMT. Three patients are alive without disease 14, 36 and 45 months post BMT with Karnofsky scores of 100%. The actuarial 3-year probabilities of relapse and disease-free survival were 0.54 and 0.19, respectively. We concluded that a PMRD graft is a viable option, comparable to the use of matched related or unrelated donors, in patients with PIF AML in whom time is of the essence.

Acute Disease↗
PubMed2001

Partially mismatched related donor bone marrow transplantation as salvage for patients with AML who failed autologous stem cell transplant.

Treatment options for patients who relapse are limited and the outcome is dismal. Between August 1993 and January 1999, 17 patients, median age 26 (4-44) years, underwent T cell depleted bone marrow transplant from partially mismatched related donors (PMRD), as a salvage for AML relapsing after an autograft. The median time from auto-transplant to relapse was 7 months (1.5-24) and the interval between transplants was 10 months (3-30). All patients had active leukemia at time of transplant. Donors were siblings (n = 8), parents (n = 2), daughters (n = 4) and others (n = 3), and 82% were > or = 2 major HLA antigen mismatched with the recipient. The conditioning therapy included total body irradiation in 14 patients and was busulfan-based in three. Graft-versus-host disease (GVHD) prophylaxis consisted of partial T cell depletion along with post-transplant immunosuppression. Median day to engraftment was 16 days (12-20). Acute GVHD was seen in six patients, and chronic GVHD in four of 13 surviving beyond 100 days. Ten patients died of non-relapse causes, at 1-588 (median 77) days. Two patients relapsed at 3 and 4 months. Five patients (29%) are surviving leukemia-free 42-84 months post transplant (median 68 months). A short interval between transplants was predictive of early relapse but not mortality. Age <18 and <2 organ toxicities were marginally predictive of better survival. We conclude that BMT from PMRD is a reasonable option for patients with refractory AML post autograft.

Acute Disease↗
PubMed2001

Therapeutic vaccination (p24-VLP) of patients with advanced HIV-1 infection in the pre-HAART era does not alter CD4 cell decline.

In a randomized placebo controlled trial 304 HIV infected patients with CD4 cell counts below 350 cells/microL received therapeutic vaccination with: alum placebo (Group I, n = 102), p24-VLP 500 microg (Group II, n = 101) or p24-VLP 1000 microg (Group III, n = 101) p24-VLP monthly for six months. Over one year the average change in CD4 cell count did not differ significantly between groups (-32, -40 and -52 cells per microL respectively). There was also no difference between groups in progression to CDC category B or C events, or in adverse events. Therapeutic vaccination with p24-VLP does not affect CD4 cell decline in patients with advanced HIV infection.

AIDS Vaccines↗
PubMed2001

The -590C/T and -34C/T interleukin-4 promoter polymorphisms are not associated with atopic eczema in childhood.

Susceptibility to the development of asthma and other atopic diseases is known to have a genetic component. To date, several studies have linked chromosome 5q31 to asthma and atopy in human beings. This region harbors a cluster of cytokine and growth factor genes, IL-4 presenting as a prime atopy candidate gene, inasmuch as it plays a pivotal role in the atopy pathway. Our approach was to identify polymorphisms within the promoter regions of IL-4 and test their association with atopic eczema. Polymorphisms were typed in a cohort of 76 small nuclear families and 25 triads with childhood atopic eczema. The genotypes were used to test for linkage in the presence of association with atopic eczema. A new polymorphism, -34C/T, was identified and studied with a known polymorphism, -590C/T. On its own, each polymorphism showed no association with atopic eczema. The 2 polymorphisms were used to generate haplotypes, and a significant result was found for the -590C/-34C haplotype. However, after Bonferroni correction for multiple testing, the association became nonsignificant. Neither polymorphism predisposes to early-onset atopic eczema by itself, but suggestive linkage was found for the -590C/-34C haplotype in this study.

Child↗
PubMed2001

Validation of a commercially available monoclonal antibody-based competitive-inhibition enzyme-linked immunosorbent assay for detection of serum antibodies to Neospora caninum in cattle.

A previously described monoclonal antibody (MAb)-based competitive-inhibition enzyme-linked immunosorbent assay (cELISA) was modified to optimize performance, and the assay was validated in various defined cattle populations for detection of serum antibody to Neospora caninum, a major cause of bovine abortion. Modifications to the cELISA included capturing native N. caninum antigen with a parasite-specific MAb (MAb 5B6-25) and directly conjugating the competitor MAb (MAb 4A4-2), with both MAbs binding different epitopes of a conserved, immunodominant 65-kDa tachyzoite surface antigen. The assay was validated using three serum sets, a "gold standard" set of 184 cow sera defined by fetal histopathology and N. caninum immunohistochemistry and by maternal N. caninum indirect fluorescence assay (IFA) at a 1:200 serum dilution, a relative standard set of 330 cow sera defined by IFA alone, and a set of 4,323 cow sera of unknown N. caninum status. A test cutoff of 30% inhibition was identified. The diagnostic sensitivity was 97.6%, and diagnostic specificity was 98.6% for the gold standard abortion-defined sera. The diagnostic sensitivity was 96.4%, and diagnostic specificity was 96.8% for the relative standard IFA-defined sera. Testing of the 4,323 bovine sera of unknown N. caninum status revealed a distinct bimodal distribution and steep sigmoid frequency curve with only 1.8% of samples within 5% of the test cutoff, indicating a sharp discrimination between test-positive and test-negative samples. In summary, the modified N. caninum cELISA provided a simple, rapid, and versatile method to accurately identify N. caninum infection status in cattle using a single cutoff value.

Abortion, Veterinary↗
PubMed2001

Nephrostomy tube or 'JJ' ureteric stent in ureteric obstruction: assessment of patient perspectives using quality-of-life survey and utility analysis.

INTRODUCTION: Upper urinary tract obstruction is often relieved by either a percutaneous nephrostomy tube (PCN) or a ureteric stent. Both can cause considerable morbidity and reduce patient's health-related quality of life (QoL). We have compared the QoL in these 2 groups. PATIENTS AND METHODS: 34 patients (21 stent and 13 PCN) with unilateral ureteric obstruction were prospectively studied. Each patient completed a questionnaire, which included a common single health index (EuroQol EQ-5D) and intervention-specific questions to assess pain, urinary symptoms and day-to-day problems. RESULTS: There were 22 male and 12 female patients [mean age 56+/-9 years (PCN) and 55+/-14 years (stent)]. The mean duration between the intervention and conduct of the survey was 12+/-5 days for PCN and 28+/-14 days for stent. There was no different in the mean EuroQol score (p = 0.199) and analogue score (p = 0.596) indicating no differences in the gross defects in physical and psychosocial function and the utility between the 2 groups. There was a significant difference in the urinary symptoms (p<0.0001) with patients who had a stent experiencing significantly more irritative urinary symptoms. This group also suffered discomfort for a greater duration and in various postures requiring more analgesia (although not significant with Bonferroni correction). Patients with PCN required more help in the daily care of the nephrostomy tube. There was no difference in the incidence of infections and the need for antibiotics. CONCLUSIONS: Patients with 'JJ' stents have significantly more irritative urinary symptoms and a high chance of local discomfort than patients with nephrostomy tubes (PCN). However, based on the EuroQol analysis, there is no significant difference in the gross impact on the health-related QoL or the utility between these groups indicating no patient preference for either modality of treatment.

Adult↗
PubMed2001

Genomic imprinting in plants.

Genomic imprinting, though most extensively studied in mammals, has long been known to perform an important role in seed development in flowering plants. In this chapter, an overview of what is known to date about genomic imprinting in flowering plants and how this knowledge came into being will be given.

Genomic Imprinting↗
PubMed2000

Qualitative study of views of health professionals and patients on guided self management plans for asthma.

OBJECTIVES: To explore the views held by general practitioners, practice nurses, and patients about the role of guided self management plans in asthma care. DESIGN: Qualitative study using nine focus groups that each met on two occasions. SETTING: South Wales. SUBJECTS: 13 asthma nurses, 11 general practitioners (six with an interest in asthma), and 32 patients (13 adults compliant with treatment, 12 non-compliant adults, and seven teenagers). RESULTS: Neither health professionals nor patients were enthusiastic about guided self management plans, and, although for different reasons, almost all participants were ambivalent about their usefulness or relevance. Most professionals opposed their use. Few patients reported sustained use, and most felt that plans were largely irrelevant to them. The attitudes associated with these views reflect the gulf between the professionals' concept of the "responsible asthma patient" and the patients' view. CONCLUSIONS: Attempts to introduce self guided management plans in primary care are unlikely to be successful. A more patient centred, patient negotiated plan is needed for asthma care in the community.

Adolescent↗
PubMed2000

Structure-based design of an osteoclast-selective, nonpeptide src homology 2 inhibitor with in vivo antiresorptive activity.

Targeted disruption of the pp60(src) (Src) gene has implicated this tyrosine kinase in osteoclast-mediated bone resorption and as a therapeutic target for the treatment of osteoporosis and other bone-related diseases. Herein we describe the discovery of a nonpeptide inhibitor (AP22408) of Src that demonstrates in vivo antiresorptive activity. Based on a cocrystal structure of the noncatalytic Src homology 2 (SH2) domain of Src complexed with citrate [in the phosphotyrosine (pTyr) binding pocket], we designed 3',4'-diphosphonophenylalanine (Dpp) as a pTyr mimic. In addition to its design to bind Src SH2, the Dpp moiety exhibits bone-targeting properties that confer osteoclast selectivity, hence minimizing possible undesired effects on other cells that have Src-dependent activities. The chemical structure AP22408 also illustrates a bicyclic template to replace the post-pTyr sequence of cognate Src SH2 phosphopeptides such as Ac-pTyr-Glu-Glu-Ile (1). An x-ray structure of AP22408 complexed with Lck (S164C) SH2 confirmed molecular interactions of both the Dpp and bicyclic template of AP22408 as predicted from molecular modeling. Relative to the cognate phosphopeptide, AP22408 exhibits significantly increased Src SH2 binding affinity (IC(50) = 0.30 microM for AP22408 and 5.5 microM for 1). Furthermore, AP22408 inhibits rabbit osteoclast-mediated resorption of dentine in a cellular assay, exhibits bone-targeting properties based on a hydroxyapatite adsorption assay, and demonstrates in vivo antiresorptive activity in a parathyroid hormone-induced rat model.

Adsorption↗
PubMed2000

Increasing the potency of MHC class II-presented epitopes by linkage to Ii-Key peptide.

We previously found that peptide Ii77-92 from the immunoregulatory Ii protein significantly enhances the binding of antigenic peptides to MHC class II molecules. Now a series of hybrids have been constructed linking LRMK, the active core region of the Ii77-92 peptide, to an antigenic epitope of cytochrome C. In vitro T cell hybridoma stimulation by some of these hybrids is up to 250 times more potent than by the antigenic peptide. The biological activities of the hybrids were tested in terms of length and composition of the linker. Simple spacers containing a polymethylene bridge (-HN-CH(2)-CH(2)-CH(2)-CH(2)-CO(2)-) were fully active in these hybrids which can enhance vaccination with MHC class II-presented epitopes.

Amino Acid Sequence↗
PubMed2000

Determining ionic conductivity from structural models of fast ionic conductors

Reverse Monte Carlo produced structural models of silver ion conducting glasses and crystals have been investigated by the bond-valence technique. Both absolute ionic conductivity and activation energy can be determined directly from the "pathway volume" of the structural models, i.e., from the volume fraction of the percolating pathway cluster. This pathway volume-conductivity relation was found to hold for glassy and crystalline systems with silver ion conductivities differing by more than 11 orders of magnitude. Earlier, less universal rules were rationalized and unified by means of this approach.

Journal Article↗
PubMed2000

The radiologist says malrotation: does the surgeon operate?

The management of malrotation when it is an incidental finding is unclear. This retrospective study reports an analysis of radiological and operative findings in a series of 71 patients. There were no deaths. We report a false-positive rate of 15% for upper gastrointestinal contrast studies reported as showing malrotation. Our findings and a review of the literature demonstrate that in the asymptomatic child over 2 years of age, the evidence supporting mandatory correction of malrotation is weak.

Child, Preschool↗
PubMed2000

High sensitivity and specificity of a laboratory-based serological test, pylori DTect ELISA, for detection of Helicobacter pylori infection.

A number of commercial ELISA kits are now available for detection of Helicobacter pylori infection. Generally, whereas the manufacturers have claimed high sensitivity and specificity, independent studies have often failed to confirm the results. The aim of this study was to independently evaluate the pylori DTect ELISA, a commercial kit for detection of H. pylori infection, in Australian patients with dyspepsia and reflux symptoms. Two hundred and nine consecutive patients (102 males and 107 females, mean age 52.8 years) who were referred for endoscopy due to upper gastrointestinal symptoms, but had not received anti-H. pylori therapy were enrolled. A 10 mL blood sample was obtained from each subject and used to evaluate the kit. The absorbance index (AI) was calculated from the mean of two readings of optical density (OD) of each serum sample. Eight biopsies from the gastric antrum (x3), body (x2), fundus (x2), and incisura (x1) were obtained from each patient for CLO-testing (x1), culture (x3), and histological examination (x4) for H. pylori. Overall, 84 (40.2%) patients were infected with H. pylori as determined by the biopsy-based "gold standard." The AIs ranged from 0 to 1.86; 0.12 to 1.86 in H. pylori positive patients and 0 to 1.49 in negative patients. The pylori DTect ELISA obtained an accuracy of 94 to 95% under AI ranges between 0.20 to 0.40, with the highest accuracy being 95% under AIs of 0.25 and 0.35. An AI of 0.25 was recommended as the best cut-off AI, with a sensitivity of 96.4%, specificity of 93.6%, positive predictive value of 91% and negative predictive value of 97.5%. It is concluded that the pylori DTect ELISA is accurate for detecting H. pylori infection in patients with dyspepsia and reflux symptoms in Australia, when an AI of 0.25 is taken as the cut-off value.

Adolescent↗
PubMed2000

Organelle pH studies using targeted avidin and fluorescein-biotin.

BACKGROUND: Mammalian organelles of the secretory pathway are of differing pH. The pH values form a decreasing gradient: the endoplasmic reticulum (ER) is nearly neutral, the Golgi is mildly acidic and the secretory granules are more acidic still ( approximately pH 5). The mechanisms that regulate pH in these organelles are still unknown. RESULTS: Using a novel method, we tested whether differences in H(+) 'leak' and/or counterion conductances contributed to the pH difference between two secretory pathway organelles. A pH-sensitive, membrane-permeable fluorescein-biotin was targeted to endoplasmic-reticulum- and Golgi-localized avidin-chimera proteins in HeLa cells. In live, intact cells, ER pH (pH(ER)) was 7.2 +/- 0.2 and Golgi pH (pH(G)) was 6.4 +/- 0.3 and was dissipated by bafilomycin. Buffer capacities of the cytosol, ER and Golgi were all similar (6-10 mM/pH). ER membranes had an apparent H(+) permeability three times greater than that of Golgi membranes. Removal of either K(+) or Cl(-) did not affect ER and Golgi H(+) leak rates, or steady-state pH(G) and pH(ER). CONCLUSIONS: The Golgi is more acidic than the ER because it has an active H(+) pump and fewer or smaller H(+) leaks. Neither buffer capacity nor counterion permeabilities were key determinants of pH(G), pH(ER) or ER/Golgi H(+) leak rates.

Avidin↗
PubMed2000

Esophageal histology does not provide additional useful information over clinical assessment in identifying reflux patients presenting for esophagogastroduodenoscopy.

We prospectively evaluated the value of histology in identifying gastroesophageal reflux disease (GERD) in consecutive patients enrolled for upper endoscopy. GERD was defined as heartburn occurring at least weekly. Macroscopic esophagitis was graded and an esophageal biopsy was taken 2 cm above the gastroesophageal junction. Histological esophagitis was identified by: (1) basal cell hyperplasia >15%, (2) increased papillary length >66%, and (3) infiltration by leukocytes/eosinophils. The sensitivity, specificity, and positive and negative predictive value of histological esophagitis in patients with and without typical reflux symptoms, with and without endoscopic changes, or both were evaluated. Of 178 patients, reflux symptoms were present in 59% (N = 105) and esophageal erosions in 19% (N = 34); 75 patients had reflux symptoms but no erosions. While the specificity of histology was adequate (78%), it was insensitive (30%). The positive and negative predictive values were 67% and 44%, respectively. No single individual parameter was better than any other. Thus, histology appears to be of no additional value in identifying GERD.

Endoscopy, Digestive System↗