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Biomedical subjects

R Thomas

Publications and source records attributed to R Thomas.

At least 217 records · Page 12Linked to original sources
PubMed1999

Tumor metastasis biopsy as a surrogate marker of response to melanoma immunotherapy.

In patients undergoing immunotherapy for metastatic melanoma, the clinical response in immunotherapeutic trials may be partial or difficult to detect. Tumor metastasis biopsy allows direct characterisation of an anti-tumor immunological response. During a phase I/II trial of granulocyte macrophage colony stimulating factor (GM-CSF) transduced autologous melanoma immunotherapy, the cellular response was examined by immunohistochemical analysis in a limited number of tumor biopsies taken from patients who either responded or progressed. Clinical response was associated with tumor infiltration by CD4+ and CD8+ T-cells, macrophages and differentiated dendritic cells (DC), and expression of HLA-DR by the tumor cells. This tumor infiltration was associated with increased melanoma-specific peripheral blood precursor cytotoxic T-lymphocyte (pCTL) and the ability to obtain tumor-infiltrating lymphocytes in vitro. In contrast, progression or a lack of clinical response was associated with a lack of T-cell and DC infiltration into the tumor tissue in all such biopsies. Macrophages and eosinophils infiltrated these tumors, while T-cells and DC were present at some distance from the tumor. These preliminary data strongly suggest that the location and extent of T-cell and DC infiltration, as well as the expression of HLA-DR by tumor cells are associated with a clinical response in this form of melanoma immunotherapy.

Adult↗
PubMed1999

Identification of mutations in the repeated part of the autosomal dominant polycystic kidney disease type 1 gene, PKD1, by long-range PCR.

We have used long-range PCR to identify mutations in the duplicated part of the PKD1 gene. By means of a PKD1-specific primer in intron 1, an approximately 13.6-kb PCR product that includes exons 2-15 of the PKD1 gene has been used to search for mutations, by direct sequence analysis. This region contains the majority of the predicted extracellular domains of the PKD1-gene product, polycystin, including the 16 novel PKD domains that have similarity to immunoglobulin-like domains found in many cell-adhesion molecules and cell-surface receptors. Direct sequence analysis of exons encoding all the 16 PKD domains was performed on PCR products from a group of 24 unrelated patients with autosomal dominant polycystic kidney disease (ADPKD [MIM 173900]). Seven novel mutations were found in a screening of 42% of the PKD1-coding region in each patient, representing a 29% detection rate; these mutations included two deletions (one of 3 kb and the other of 28 bp), one single-base insertion, and four nucleotide substitutions (one splice site, one nonsense, and two missense). Five of these mutations would be predicted to cause a prematurely truncated protein. Two coding and 18 silent polymorphisms were also found. When, for the PKD1 gene, this method is coupled with existing mutation-detection methods, virtually the whole of this large, complex gene can now be screened for mutations.

Base Sequence↗
PubMed1999

Preoperative antibiotics and steroids in vestibular schwannoma excision.

OBJECTIVE: To examine the benefits of preoperative admission for intravenous steroids and antibiotics for patients undergoing vestibular schwannoma excision. STUDY DESIGN: Retrospective cohort study. METHODS: One hundred twenty patients with pathologically confirmed vestibular schwannoma followed for at least 1 year after surgery were included. Sixty patients were assigned to the preoperative admission group and 60 patients to the same-day-admission surgery group. The preoperative admission group was given intravenous dexamethasone (0.1 mg/kg) and intravenous cefazolin (1 g) beginning 12 hours before surgery. The same-day-surgery group received the same dosage of medication beginning at induction of anesthesia. OUTCOMES: Facial nerve function, meningitis, and wound infection rates, duration of hospital stay, and readmission rates were examined. RESULTS: There was no statistical difference in facial nerve function between the groups when controlling for tumor size. Likewise, there was no difference in meningitis or wound infection rates in the groups. As expected, hospital stay was significantly reduced but readmission rates were not affected. CONCLUSIONS: There are no apparent facial nerve function or infection control benefits to 1-day preoperative admission for intravenous steroids and antibiotics for patients undergoing vestibular schwannoma excision.

Anti-Bacterial Agents↗
PubMed1999

Immature human monocyte-derived dendritic cells migrate rapidly to draining lymph nodes after intradermal injection for melanoma immunotherapy.

Injected antigen-loaded immature monocyte-derived dendritic cells (DCs) may be incapable of migrating from skin to draining lymph nodes for antigen presentation. The in vivo migratory capacity of intradermally administered immature monocyte-derived DCs was therefore investigated during a phase I/II clinical trial for metastatic melanoma. DCs cultured from adherent monocytes in the presence of autologous serum, granulocyte-macrophage colony stimulating factor and interleukin-4 were pulsed with antigen and labelled with technetium-99m hexamethylpropylene-amineoxime (99mTc-HMPAO) ex vivo, then injected intradermally. A 99mTc-HMPAO control containing an equivalent amount of radioactivity was injected into the opposite thigh. The pelvis was then imaged with a gamma camera. The DCs were characterized as immature by functional and phenotypic analysis. Labelled DCs travelled to the draining inguinal lymph nodes within 10 min, and the draining lymph nodes were clearly outlined up to 4 h after injection. Free NmTc outlined draining lymph nodes after 10 min but was cleared from the nodes within 1 h. Thus, immature human monocyte-derived DCs migrate rapidly to and remain in draining lymph nodes after intradermal injection for immunotherapy.

Adult↗
PubMed1999

Reproduction rates in multiregion modeling systems for HIV / AIDS.

The persistence of HIV/AIDS has seen a revival of academic interest in the development of modeling systems to assist understanding the population dynamics of this infection. Moreover, it has become increasingly recognized that a key component of these systems for interpreting disease prevention is their reproduction rate, which provides an indication of whether an epidemic might start in a community described by a particular set of epidemiological characteristics. The properties of these rates have been explored in detail for models of a single risk behavior but not for multiregion formats that allow for the transfer of infection between geographical units. Therefore, in this paper the author derives reproduction rates for a multiregion HIV/AIDS model together with their associated critical thresholds that estimate the minimum population of susceptibles necessary for an epidemic to begin. These statistics are interpreted for a simplified global setting representing regional variations in the potential onset of HIV/AIDS. In the discussion the author examines the potential applicability of these results to understanding HIV/AIDS prevention.

Acquired Immunodeficiency Syndrome↗
PubMed1999

A randomized, prospective study to evaluate the efficacy and acceptance of three bowel preparations for colonoscopy in children.

OBJECTIVE: We performed a prospective, randomized, single-blind study in children undergoing colonoscopy to evaluate the acceptance and efficacy of three different bowel preparations. METHODS: Seventy patients (ages 3-20 yr, 38 males) were randomly assigned to one of the three study preparations: Magnesium citrate with X-prep and clear liquid diet for 2 days (group A); Dulcolax for 2 days and Fleet enema without dietary restriction (group B); and Golytely 20 ml/kg (up to 1 L) per hour for 4 h with clear liquid diet for 1 day (group C). Endoscopists blinded to bowel preparation graded the adequacy of colon cleansing. The preparations were rated by patients for tolerance, willingness to retake them, adverse effects, and compliance. RESULTS: Data analysis using Fisher exact test and trend test showed that colon cleansing in groups A and C was superior to that in group B (p < 0.0001) and better in group C than A (p < 0.075). Overall tolerance and compliance were significantly better for groups A and B than group C (p < 0.003), but not different between A and B. More of group B patients were willing to retake the preparation than in group C (p < 0.002) and group A (p < 0.05), but this was not different between groups A and C. Adverse effects were reported more frequently by patients in group C than in groups A and B (p < 0.01). CONCLUSIONS: Although the least well tolerated, Golytely provided the best cleansing. Dulcolax without dietary restriction provided unsatisfactory colon cleansing. Magnesium citrate with X-prep was acceptable and provided good cleansing.

Adolescent↗
PubMed1999

Potential strategies utilised by papillomavirus to evade host immunity.

The co-evolution of papillomaviruses (PV) and their mammalian hosts has produced mechanisms by which PV might avoid specific and non-specific host immune responses. Low level expression of PV proteins in infected basal epithelial cells, together with an absence of inflammation and of virus-induced cell lysis, restricts the opportunity for effective PV protein presentation to immunocytes by dendritic cells. Additionally, PV early proteins, by a range of mechanisms, may restrict the efficacy of antigen presentation by these cells. Should an immune response be induced to PV antigens, resting keratinocytes (KC) appear resistant to interferon-gamma-enhanced mechanisms of cytotoxic T-lymphocyte (CTL)-mediated lysis, and expression of PV antigens by resting KC can tolerise PV-specific CTL. Thus, KC, in the absence of inflammation, may represent an immunologically privileged site for PV infection. Together, these mechanisms play a part in allowing persistence of PV-induced proliferative skin lesions for months to years, even in immunocompetent hosts.

Animals↗
PubMed1999

Genetic basis for lipopolysaccharide O-antigen biosynthesis in bordetellae.

Bordetella bronchiseptica and Bordetella parapertussis express a surface polysaccharide, attached to a lipopolysaccharide, which has been called O antigen. This structure is absent from Bordetella pertussis. We report the identification of a large genetic locus in B. bronchiseptica and B. parapertussis that is required for O-antigen biosynthesis. The locus is replaced by an insertion sequence in B. pertussis, explaining the lack of O-antigen biosynthesis in this species. The DNA sequence of the B. bronchiseptica locus has been determined and the presence of 21 open reading frames has been revealed. We have ascribed putative functions to many of these open reading frames based on database searches. Mutations in the locus in B. bronchiseptica and B. parapertussis prevent O-antigen biosynthesis and provide tools for the study of the role of O antigen in infections caused by these bacteria.

Bordetella↗
PubMed1999

DNA fingerprinting of single colonies of Helicobacter pylori from gastric cancer patients suggests infection with a single predominant strain.

In each of six gastric cancer patients, repetitive extragenic palindromic PCR DNA fingerprints of 18 single colonies of Helicobacter pylori from the gastric antrum, corpus, and cardia were identical and matched that of the parental isolate. In three additional gastric cancer patients, 17 of 18 single-colony DNA fingerprints were identical to each other and to the DNA fingerprint of the corresponding parental isolate.

Adenocarcinoma↗
PubMed1999

Zoo-FISH analysis of dog chromosome 5: identification of conserved synteny with human and cat chromosomes.

Conserved segments of synteny between the human genome and chromosome 5 (CFA 5) of the domestic dog (Canis familiaris) have been identified by reciprocal chromosome painting analysis. A CFA 5 paint probe was applied to human metaphase spreads, revealing distinct hybridisation sites on human (HSA) chromosomes 1, 11, 16, and 17. Paint probes for these human chromosomes were then hybridised to dog metaphase spreads, identifying the regions of CFA 5 with which homology is shared with the corresponding human chromosome. Application of the CFA 5 paint probe to metaphase spreads of the domestic cat (Felis catus, FCA) demonstrated hybridisation to cat chromosomes C1, D1, E1, and E2. Dog PCR primers for type 1 markers known to lie in the corresponding regions of HSA 11, 16, and 17 were used to isolate dog BAC clones representing four genes. Fluorescence in situ hybridisation analysis confirmed their localisation to CFA 5 and suggested that two of the conserved segments lie in opposing orientations on CFA 5, compared to the human chromosome concerned. A third segment appears to lie in the same orientation on both human and dog chromosomes. No suitable gene markers were available for analysis of the fourth segment. The significance of these findings is discussed with reference to current and future dog genome mapping efforts.

Animals↗
PubMed1999

Coordinated maturational regulation of PHEX and renal phosphate transport inhibitory activity: evidence for the pathophysiological role of PHEX in X-linked hypophosphatemia.

The mechanism by which inactivating mutations of PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) cause X-linked hypophosphatemia remains unknown. However, recent reports suggest errant PHEX activity in osteoblasts may fail to inactivate a phosphaturic factor produced by these cells. To test this possibility, we examined coordinated maturational expression of PHEX and production of phosphate transport inhibitory activity in osteoblasts from normal and hyp-mice. We assessed the inhibitory activity in conditioned medium by examining the effects on opossum kidney cell phosphate transport and osteoblast PHEX expression by reverse transcriptase-polymerase chain reaction during a 17-day maturational period. Inhibitory activity increased as a function of osteoblast maturational stage, with no activity after 3 days and persistent activity by 6 days of culture. More significantly, equal phosphate transport inhibitory activity in conditioned medium from normal and hyp-mouse osteoblasts (control 1.90 +/- 0.12, normal 1.48 +/- 0.10, hyp 1.45 +/- 0.04 nmol/mg of protein/minute) was observed at 6 days. However, by 10 days hyp-mouse osteoblasts exhibited greater inhibitory activity than controls, and by 17 days the difference in phosphate transport inhibition maximized (control 2.08 +/- 0.09, normal 1.88 +/- 0.06, hyp 1.58 +/- 0.06 nmol/mg of protein/minute). Concurrently, we observed absent PHEX expression in normal osteoblasts after 3 days, limited production at 6 days, and significant production by day 10 of culture, while hyp-mouse osteoblasts exhibited limited PHEX activity secondary to an inactivating mutation. The data suggest that the presence of inactivating PHEX mutations results in the enhanced renal phosphate transport inhibitory activity exhibited by hyp-mouse osteoblasts.

Animals↗
PubMed1999

Source of arousal and memory for detail.

Two questions about the relationship between arousal and memory were investigated: First, does the source of arousal influence memory, and, second, what impact does arousal have on memory for detail? In Experiment 1, physiological arousal (running or not running in place) was factorially combined with emotional arousal (viewing a neutral or an emotional slide sequence). Recognition memory was tested for gist, central detail, and background detail. Experiments 2 and 3 were similar to Experiment 1, with the exception that a cued recall task was used in Experiment 2 and physiological arousal was manipulated with stationary biking in Experiment 3. The results of these experiments indicated that physiological arousal had little impact on memory and that emotional arousal led to improvements in memory for both central and background detail. Overall, these results supported the notions that the source of arousal is an important determinant of an event's memorability (Christianson, 1992a) and that emotional arousal serves to enhance the scope of memory (i.e., flashbulb memory; Brown & Kulik, 1977).

Adult↗
PubMed1999

Panic disorder in the primary care setting: comorbidity, disability, service utilization, and treatment.

BACKGROUND: Increased medical service utilization in patients with panic disorder has been described in epidemiologic studies, although service use in primary care panic patients relative to other primary care patients is less well characterized. Inadequate recognition of panic has been shown in several primary care studies, although the nature of usual care for panic in this setting has not been well documented. This study aimed to document increased service use in panic patients relative to other primary care patients and to characterize the nature of their usual care for panic and their outcome. METHOD: Using a waiting room screening questionnaire and follow-up telephone interview with the Composite International Diagnostic Interview, we identified a convenience sample of 81 patients with panic disorder (DSM-IV) and a control group of 183 psychiatrically healthy patients in 3 primary care settings on the West Coast and determined psychiatric diagnostic comorbidity, panic characteristics, disability, and medical and mental health service use, including medications. A subsample (N = 41) of panic patients was reinterviewed 4-10 months later to determine the persistence of panic and the adequacy of intervening treatment received using the Harvard/Brown Anxiety Disorders Research Program study criteria for cognitive-behavioral therapy (CBT) and an algorithm developed by the authors for medications. RESULTS: Seventy percent of panic patients had a comorbid psychiatric diagnosis. Patients had more disability in the last month (days missed or cut down activities) (p < .01), more utilization of emergency room and medical provider visits (p < .01), and more mental health visits (p < .05). Despite the latter, only 42% received psychotropic medication, 36% psychotherapy, and 64% any treatment. On follow-up, 85% still met diagnostic criteria for panic, and only 22% had received adequate medication (type and/or dose) and 12% adequate (i.e., CBT) psychotherapy. CONCLUSION: These findings suggest a need for improved treatment interventions for panic disorder in the primary care setting to decrease disability and potentially inappropriate medical service utilization.

Adult↗