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Biomedical subjects

S Bell

Publications and source records attributed to S Bell.

At least 55 records · Page 3Linked to original sources

DLA-DQA1 polymorphisms in dogs defined by sequence-specific oligonucleotide probes (SSOP).

Several recent studies have identified DNA sequences for alleles of the DLA-DQA1 locus in the dog. To date, 10 DQA1 alleles have been reported. No data exists on the frequencies of these alleles within the general dog population, nor is there any indication of whether alleles are breed specific. We have addressed this issue by establishing a molecular-based sequence-specific oligonucleotide probing (SSOP) method to identify all published DQA1 alleles and have used these methods to type a large number of dogs. Oligonucleotide probes were designed to detect all the polymorphic sites in exon 2. This allowed assignment at the allele level. Three hundred and thirty dogs were typed for DQA1. All but two of the published DQA1 alleles were identified in these animals. One new allele was identified, and confirmed by DNA cloning and sequencing. This typing method provides a powerful tool for generating data that will be essential for studies investigating the genetic relationships between different breeds.

Animals↗

Identification of further DLA-DRB1 and DQA1 alleles in the dog.

Three novel DLA-DRB1 alleles and one novel DQA1 allele have been identified in a panel of 367 dogs. These were suggested by unusual reaction patterns found in sequence specific oligonucleotide probing (SSOP) data. Four new alleles were confirmed using DNA cloning and sequencing.

Alleles↗

The correlation between presenting ST-segment depression and the final size of acute myocardial infarcts in patients with acute coronary syndromes.

The use of reperfusion therapy in patients with ST elevation acute coronary syndromes had been established. However, reperfusion therapy is usually considered contra-indicated in those with ST depression, despite the knowledge that regional posterior infarction is typically indicated by ST depression maximal in leads V1 to V3 and nonregional subendocardial infarction is typically indicated by marked ST depression maximal in other leads. This study of patients with non-ST-elevation acute coronary syndromes investigates the quantitative relationship between presenting ST depression and final QRS changes in both of these subgroups. The final QRS score was significantly higher (2.44 points) than that of a control group with not ST depression, (1.55 points) in the group with maximal ST depression in V1 to V3 (P = 0.04). However, in the entire population, there was a highly significant correlation (P = .003) between the sum of the presenting ST depression and the final QRS score. Trials of reperfusion therapy will be required to determine if such evolution to electrocardiogram documented acute myocardial infarction can be prevented in patient with marked ST depression acute coronary syndromes.

Case-Control Studies↗

Mucormycosis: a case study.

Throughout the history of mucormycosis, from the first case in humans reported in 1885 by Paltauf, through publication by Gregory et al of the first observation of rhino-orbital cerebral mucormycosis in 1943, to the report by Harris in 1955 of the first known survivor, little has changed in the diagnosis and outcome of this disease. Although mucormycosis of any form--cerebral, cutaneous, rhinocerebral, intestinal, or pulmonary--is still a rarity, it should be suspected in patients who are diabetic or immunocompromised. Administration of amphotericin B, surgical debridement of infected tissue, correction of the underlying cause, and use of adjunctive HBO therapy remain the standard treatments.

Adult↗

Activation and adoptive transfer of Epstein-Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease.

The treatment of Epstein-Barr virus (EBV)-associated lymphoproliferative disease (PTLD) in EBV seronegative solid organ transplant recipients who acquire their EBV infection after engraftment poses a considerable challenge because of underlying immunosuppression that inhibits the virus-specific cytotoxic T cell (CTL) response in vivo. We have developed a protocol for activating autologous EBV-specific CTL lines from these patients and show their potential use for immunotherapy against PTLD in solid organ transplant patients. Peripheral blood mononuclear cells from a panel of solid organ transplant recipients with and without active PTLD were used to assess EBV-specific memory CTL responses. The activation protocol involved cocultivation of peripheral blood mononuclear cells with an autologous lymphoblastoid cell line under conditions that favored expansion of virus-specific CTL and hindered the proliferation of allospecific T cells. These CTL consistently showed (i) strong EBV-specificity, including reactivity through defined epitopes in spite of concurrent immunosuppressive therapy, and (ii) no alloreactivity toward donor alloantigens. More importantly, adoptive transfer of these autologous CTLs into a single patient with active PTLD was coincident with a very significant regression of the PTLD. These results demonstrate that a potent EBV-specific memory response can be expanded from solid organ recipients who have acquired their primary EBV infection under high levels of immunosuppressive therapy and that these T cells may have therapeutic potential against PTLD.

Adoptive Transfer↗

Interbreed variation of DLA-DRB1, DQA1 alleles and haplotypes in the dog.

Although 36 DLA-DRB1 and 10 DLA-DQA1 allele sequences have been published to date, no data on individual allele frequencies exists, either for specific breeds or cross breeds, and the full extent of the polymorphism at each of these loci is still not known. We have used sequence-specific oligonucleotide probing (SSOP) to characterise a series of 367 dogs for their DRB1 and DQA1 alleles. These included individual animals from over 60 different breeds, with numbers per breed ranging from 1 to 39. DLA types were generated from 218 dogs for DRB1 and from 330 dogs for DQA1, while 181 dogs were characterised for both these loci. The frequency of individual DRB1 and DQA1 alleles showed considerable interbreed variation, e.g. 83% of West Highland White Terriers were DRB1*01 as opposed to 9% of Collies. No breed had >9 of the 22 DRB1 types defined in this study; several breeds had only two DRB1 types. DLA-DQA1 showed less variation in allele numbers per breed, but also showed considerable interbreed frequency variation. Haplotype analysis revealed over 44 different DRB1/DQA1 combinations. Of these, 25 were in a number of animals, and also in an animal that was homozygous for one or both of these loci. Some DRB1 alleles could be found in combination with several different DQA1 alleles, while others were only present in one haplotypic combination. DLA allele frequency data in normal dogs will be critical for disease association studies. It may also be possible to use haplotype data to establish the genetic relationships between different dog breeds.

Alleles↗

Classification of ion mobility spectra by functional groups using neural networks.

Neural networks were trained using whole ion mobility spectra from a standardized database of 3137 spectra for 204 chemicals at various concentrations. Performance of the network was measured by the success of classification into ten chemical classes. Eleven stages for evaluation of spectra and of spectral pre-processing were employed and minimums established for response thresholds and spectral purity. After optimization of the database, network, and pre-processing routines, the fraction of successful classifications by functional group was 0.91 throughout a range of concentrations. Network classification relied on a combination of features, including drift times, number of peaks, relative intensities, and other factors apparently including peak shape. The network was opportunistic, exploiting different features within different chemical classes. Application of neural networks in a two-tier design where chemicals were first identified by class and then individually eliminated all but one false positive out of 161 test spectra. These findings establish that ion mobility spectra, even with low resolution instrumentation, contain sufficient detail to permit the development of automated identification systems.

Alcohols↗

DLA-DRB1 polymorphisms in dogs defined by sequence-specific oligonucleotide probes (SSOP).

To date, DNA sequences for 29 dog DLA-DRB1 alleles have been reported. However, no data exists on the frequencies of these alleles within the general dog population, nor is there any indication of whether there is interbreed variation of allele distribution. We have addressed this by establishing a molecular based sequence-specific oligonucleotide probing (SSOP) method to identify all of the known broad DRB1 types and we have used this to type a random panel of dogs. A series of oligonucleotide probes were designed to detect known polymorphisms in the three DRB1 hypervariable regions, together with two distinctive motifs in other regions of exon 2. This set of probes enabled us to assign broad DRB1 types. Two hundred and eighteen dogs were SSOP typed for DRB1. All but 4 of the published DLA-DRB1 alleles were identified in these animals. Interbreed variation in both allele distributions and allele frequencies were observed, which may be useful in the study of genetic variation between breeds. This variation also has implications for the selection of control groups for studies aimed at identifying MHC associations with disease susceptibility in the dog.

Animals↗

Effect of beta-glucan from oats and yeast on serum lipids.

Heart disease is the leading cause of death in the U.S. One way to reduce the risk of developing the disease is to lower serum cholesterol levels by making dietary changes. In addition to reducing intake of total fat, saturated fat, and dietary cholesterol, serum cholesterol can be further reduced by added fiber, especially from sources rich in beta-glucan. In this review, two sources of beta-glucan are described; one source is oats and the other yeast. Their chemical structures and physical properties are compared, and their effect on serum lipid levels is described. Oat beta-glucans are found in various breakfast cereals and snacks. Usually, several servings of these products are required to meet the Food and Drug Administration's claim of reducing the risk of heart disease. The yeast-derived fiber is a more concentrated source of beta-glucan than the oat product. It is currently being tested in a wide variety of food products.

Avena↗

A case of acute renal failure and compartment syndrome after an alcoholic binge.

A 25 year old man presented with anuria and bilateral leg pain two days after an alcoholic binge. He subsequently developed rhabdomyolysis causing acute renal failure, with compartment syndrome of both lower legs. This required urgent dialysis and fasciotomy respectively within six hours of admission. He remained dialysis dependent for three weeks and only after four months was he able to weight bear on both legs. Alcohol is a leading cause of rhabdomyolysis. Early recognition and prompt treatment is essential to prevent serious complications.

Acute Kidney Injury↗

Nerve entrapment syndromes as a cause of pain in the hip, groin and buttock.

In sports medicine, chronic hip, groin and buttock pain is a common diagnostic problem. Because of the complex anatomy of this region and the many potential neurological causes for pain, few sports clinicians have a detailed understanding of this problem. This paper discusses the clinical aspects of nerve entrapment syndromes related to sport and takes a regional approach in order to provide a diagnostic framework for the general sports physician. The various neurological syndromes are discussed and the surgical management elaborated in detail. For some specific conditions, such as the so-called 'piriformis syndrome', the pathophysiological understanding has changed since the early descriptions and now this particular diagnosis is often ascribed to almost any cause of buttock and/or hamstring symptoms. We discuss the nature of the origin of local symptoms and note that the often described symptoms are more likely due to compression of structures other then the sciatic nerve. Furthermore, the role of piriformis hypertrophy or anatomical nerve variations in the genesis of this syndrome must be questioned. We suggest renaming this the 'deep gluteal syndrome' to account for all of the observed phenomena. As sports medicine continues to develop a scientific basis, the role of nerve entrapments as the basis for chronic symptomatology is undergoing a new understanding and clinicians need to be aware of the diagnostic possibilities and be able to advise patients accordingly on the basis of scientific fact not anecdotal fiction.

Buttocks↗

Sterilization of contaminated bone-tendon autografts using 10% povidone-iodine solution.

This study evaluates methods of sterilizing contaminated bone-tendon autografts using 10% povidone-iodine solution. Sterile grafts were prepared from human cadavers. Grafts were immersed in a suspension of either Staphylococcus aureus or Pseudomonas aeruginosa, and three sets of sterilization experiments were performed in 10% povidone-iodine for 30 minutes: one each with S. aureus and P. aeruginosa by static soaking and a third with S. aureus by serial washing with agitation. Of grafts inoculated with S. aureus, six of six grew the test organism after soaking at room temperature, as did five of six after soaking at 36 degrees C and also eight of nine after washing with agitation. Of grafts inoculated with P. aeruginosa, five of six grew the test strain after soaking at room temperature, as did six of six after soaking at 36 degrees C. Thirty minutes of exposure to aqueous 10% povidone-iodine does not adequately sterilize an inoculated graft.

Anti-Infective Agents, Local↗

Obturator neuropathy. An anatomic perspective.

Entrapment of the anterior division of the obturator nerve is a recently described cause of medial groin pain. This anatomic study examines the extrapelvic course of the nerve and related fascia in the adductor region to provide an anatomic basis for the syndrome and to aid in surgical treatment. Twelve anatomic specimen limbs were dissected to document the extrapelvic course of the obturator nerve, the myofascial arrangement, and the vasculature. A thirteenth limb was prepared with intraarterial glycerin to examine the vessels in more detail. A distinct fascial plane was found deep to the adductor longus and pectineus overlying the anterior division of the obturator nerve. The arterial supply to the adductor muscles is related intimately to the nerve and its branches, with associated local thickening of the fascial connective tissue. The relationship between the nerve, vessels, and fascia appears sufficient to result in an entrapment syndrome. The anatomic findings from this series will help plan the surgical treatment of this condition.

Cadaver↗

Blood-brain barrier disruption for the treatment of malignant brain tumors: The National Program.

Chemotherapy delivery for the treatment of malignant brain tumors is markedly enhanced when given in conjunction with osmotic opening of the blood-brain barrier. Osmotic opening or disruption of the blood-brain barrier is achieved while the patient is under general anesthesia, by the infusion of mannitol into the internal carotid or vertebral artery circulation. The mannitol infusion is followed by administration of intraarterial chemotherapy. A National Blood-Brain Barrier Program now exists and includes six universities. Within the National Program over 4200 blood-brain barrier disruption procedures have been performed in over 400 patients. Patients with primary central nervous system (CNS) lymphoma, glioma, primitive neuroectodermal tumor (PNET), germ cell and metastatic cancer are eligible for treatment. Results in patients with primary CNS lymphoma, recently reported in the Cancer Journal, include the first example of a durable response in a primary brain tumor without loss of cognitive function and without use of radiotherapy. Results with PNET and germ cell tumors are also very encouraging. Advanced practice nurses coordinate the care of blood-brain barrier disruption patients. Care includes patients selection, education, close neurological observation, maintenance of fluid and electrolyte balance and managing effects of high-dose chemotherapy. Both acute and long-term medical and psychological follow-up are an essential component of the program, as well as patient and family support.

Antineoplastic Agents↗