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Biomedical subjects

R Thomas

Publications and source records attributed to R Thomas.

At least 163 records · Page 9Linked to original sources
PubMed2000

A comparison of neonatal and adult multiorgan failure in a rat model.

BACKGROUND/PURPOSE: To establish a neonatal animal model of multiorgan failure (MOF) for the histological study of the sequence and severity of neonatal MOF in comparison to a model of adult MOF. METHODS: Neonatal and adult Sprague-Dawley rats received a single intraperitoneal injection of the inflammatory agent Zymosan. Rats were weighed; randomly killed on days 1 through 6; and heart, lung, liver, kidney, spleen, and ileocecum harvested for histological examination. RESULTS: Neonatal animals receiving Zymosan showed a significant increase in total body weight not seen in adults. The sequence and severity of MOF-induced organ damage were strikingly different in adult and neonatal animals. Mild lung damage was seen as early as day 1 in adult rats receiving Zymosan. This progressed to moderate damage by day 2 and severe damage by day 6. Lungs of neonatal rats receiving Zymosan showed only mild damage by day 4, which had progressed no further by day 6. Mortality rate was not significantly different between adult and neonatal animals receiving Zymosan. CONCLUSIONS: Zymosan can be used in a neonatal animal model to incite MOF. In the neonatal animal model of MOF there is (1) substantial early capillary leak as shown by increased body weight; (2) a unique progression of organ involvement-liver, kidney, lung compared with adult animals with MOF-lung, liver, kidney; and (3) relative sparing of the lung from injury. These findings are consistent with previous clinical observations of a difference in neonatal and adult MOF.

Age Factors↗
PubMed2000

Luminal contents of benign and malignant prostatic glands: correspondence to altered secretory mechanisms.

Recent changes in tissue fixation strategy, using glutaraldehyde, have clarified the secretory mechanisms of the normal prostate identifying cytoplasmic prostatic secretory granules, structures not preserved by formalin fixation. This normal secretory mechanism was absent in most adenocarcinomas, depicting an important metabolic change in transformed prostate cells. The current study further investigates differences between benign and malignant prostate secretion and relates them to the production of corpora amylacea by benign glands and crystalloids or mucin by cancer. In all normal prostate cells examined (6 cases), prostate secretory granules (PSG) were approximately 1-microm, brightly eosinophilic granules filling the cytoplasm of secretory cells and released in packets by a specialized apocrine cell structure. After apocrine decapitation and luminal dispersal, some of the cytoplasmic and PSG remnants condensed to form eosinophilic bodies (EB) with a glycoprotein rim and central protein core. EB were observed adsorbing and layering onto the surface of prostatic corpora amylacea representing their chief mode of enlargement. Biochemical analysis and x-ray diffraction studies confirmed sulfated glycosaminoglycans of similar structure as the main constituent of both PSG and corpora amylacea. Peripheral zone amphiphilic "dark cell" carcinoma (9 cases) contained almost no PSG, and showed neither apical decapitation nor EB formation, but mucin secretion was frequently detected. Crystalloids that share the same staining characteristics and sulfur content as PSG and corpora amylacea were identified in 3 selected "clear cell" carcinomas, all of which showed at least focal PSG secretion. The recognition of these differing secretory mechanisms and their deviation from normal further defines the histological criteria and spectrum of prostate malignancy.

Acid Phosphatase↗
PubMed2000

Successful defibrillation in profound hypothermia (core body temperature 25.6 degrees C).

We report a case of successful defibrillation in a severely hypothermic patient with a core body temperature of 25.6 degrees C as measured oesophageally. Ventricular fibrillation is a recognised life threatening arrhythmia in severely hypothermic patients. The traditional wisdom is that this arrhythmia is refractory to defibrillation at temperatures below 28 degrees C.

Acute Disease↗
PubMed2000

Surface markers and transendothelial migration of dendritic cells from elderly subjects.

Age-related changes of immune functions have been extensively investigated in both humans and animal models; nevertheless, the literature on potential alterations of dendritic cells, potent antigen presenting cells responsible for initiating immune responses, with aging is very scarce. We studied the immuno-phenotype of peripheral blood dendritic cells of elderly and young subjects by three-color flow cytometry. In addition, the capacity of transendothelial migration, an important step in inflammatory reactions, of peripheral blood dendritic cells of elderly subjects was investigated in an in vitro model. The expression of HLA-DR in the peripheral blood dendritic cells of the elderly subjects was significantly decreased when compared to the young control subjects. The expression of various other surface markers was similar in the young and elderly subjects. The ability of transendothelial migration of dendritic cells was found to be unimpaired in the elderly subjects. Both in the young and elderly subjects a significantly higher expression of CD29, CD86, HLA-DR, and HLA-DQ in the dendritic cells that had migrated through the endothelium in comparison to nonadherent, nonmigrating cells was found. In the migrating dendritic cells of the elderly subjects a significantly increased expression of CD11c was observed, whereas the expression of CD54 was significantly enhanced in the migrating dendritic cells of the young subjects only. In conclusion, our results demonstrate intact functions and a normal immunophenotype of dendritic cells derived from elderly subjects. Dendritic cells thus seem to be functional and therefore are not responsible for the well-known decline of T cell functions with aging.

Aged↗
PubMed2000

A mathematical model for storage and recall functions in plants.

In plantlets of Bidens pilosa L., under severely limiting environmental conditions the growth of the buds at the axil of the cotyledons (cotyledonary buds) is asymmetric (i.e. one of the buds starts growing before the other one), this asymmetry being oriented by the pricking of one of the cotyledons (i.e. pricking one cotyledon increases the probability that the bud at the axil of the other cotyledon be the first to start to grow). As long as the plant apex (i.e. the terminal bud) is present, the growth of the cotyledonary buds is inhibited (apical dominance), but the souvenir of the asymmetric message caused by sub-optimal environmental conditions and the orientation given by the cotyledon pricking is always present in the plant and can be revealed by removing the apex. Depending on the conditions for removing the plant apex and/or on the application of a variety of symmetrical treatments (e.g. thermal treatment, symmetrical pricking treatments, etc.) the stored asymmetry will either take effect (the bud at the axil of the non-pricked cotyledon will be the first to start to grow more often than the other one) or not (both buds will have equal chance to be the first to start to grow). This has been termed 'recalling' the stored asymmetry. By combining several successive symmetrical treatments, it is possible to reversibly switch on and off the recall function several times. This recall of the stored plant-asymmetry is analogous to the evocation function of a memory system. In this paper, we will present first a discrete logical version of the observed interaction structure between the main components of the bud growth system, then a continuous differential version, taking into account the main features of the observed experimental reality and trying to explain this phenomenology. The interaction structure of both the discrete and the continuous models presents similar positive and negative feedback circuits, necessary condition for observing multistationarity and stability.

Environment↗
PubMed2000

Positive feedback circuits and memory.

The concept of regulatory feedback circuit refers to oriented cyclic interactions between elements of a system. There are two classes of circuits, positive and negative, whose properties are in striking contrast. Positive circuits are a prerequisite for the occurrence of multiple steady states (multistationarity), and hence, they are involved in all processes showing hysteresis or memory. Endogenous or exogenous perturbations can lead the system to exhibit or to evoke one particular stable regime. The role of positive circuits in cell differentiation and in immunology is well documented. Negative circuits are involved in homeostatic regulation, with or without oscillations. The aim of this paper is to show: a) that positive circuits account for many features of memory stricto sensu (i.e., neural memory and mnesic evocation) as well as largo sensu (e.g. differentiation or immunological memory); and b) that simple combinations of positive and negative circuits provide powerful regulatory modules, which can also be associated in batteries. These entities have vast dynamical possibilities in the field of neurobiology, as well as in the fields of differentiation and immunology. Here we consider a universal minimal regulatory module, for which we suggest to adopt the term 'logical regulon', which can be considered as an atom of Jacob's integron. It comprises a positive and a negative circuit in its interaction matrix, and we recall the main results related to the simultaneous presence of these circuits. Finally, we give three applications of this type of interaction matrix. The first two deal with the coexistence of multiple stable steady states and periodicity in differentiation and in an immunological system showing hysteretic properties. The third deals with the dual problems of synchronization and desynchronization of a neural model for hippocampus memory evocation processes.

Cell Differentiation↗
PubMed2000

Forewarned is forearmed--benefits of preparatory information on video cassette for patients receiving chemotherapy or radiotherapy--a randomised controlled trial.

A series of UK and European audits have revealed that a high proportion of patients remain dissatisfied with the information they received following a diagnosis of cancer. Additional educational aids are often required to facilitate the consent process, and our previous work showed a high level of acceptability for video-directed information for this purpose. In this study a multidisciplinary team of health professionals worked with patients, a documentary film company and experienced television personalities to produce an information film. The aim of this study was to assess the benefits of receiving a cassette to take home following the first consultation and this was evaluated in a randomised multicentre controlled study among 220 patients receiving chemotherapy or radiotherapy over a 6-month period. There was a significant correlation between satisfaction and reduced treatment-related anxiety overall. In the video group, the mean Hospital Anxiety and Depression (HAD) anxiety score was significantly lower during treatment compared with the non-video group (4.6+/-3.7 (range: 0-18) versus 7.4+/-5.2 (range: 0-20), Chi square test P=0.001). Likewise, the mean HAD depression scores were also significantly lower in the patients prepared for the side-effects of treatment with the video (2.9+/-2.9 (range: 0-13) versus 5.3+/-4.7 (range: 0-21) Chi square test P=0.001). 81% felt the video was helpful, only 5% of patients felt this extra information was worrying. Well designed video cassettes should be regarded as a useful additional information strategy, within routine oncology practice.

Adolescent↗
PubMed2000

Effects of azide on the S(2) state EPR signals from Photosystem II.

The anion azide, N(3) (-), has been previously found to be an inhibitor of oxygen evolution by Photosystem II (PS II) of higher plants. With respect to chloride activation, azide acts primarily as a competitive inhibitor but uncompetitive inhibition also occurs [Haddy A, Hatchell JA, Kimel RA and Thomas R (1999) Biochemistry 38: 6104-6110]. In this study, the effects of azide on PS II-enriched thylakoid membranes were characterized by electron paramagnetic resonance (EPR) spectroscopy. Azide showed two distinguishable effects on the S(2) state EPR signals. In the presence of chloride, which prevented competitive binding, azide suppressed the formation of the multiline and g = 4.1 signals concurrently, indicating that the normal S(2) state was not reached. Signal suppression showed an azide concentration dependence that correlated with the fraction of PS II centers calculated to bind azide at the uncompetitive site, based on the previously determined inhibition constant. No evidence was found for an effect of azide on the Fe(II)Q(A) (-) signals at the concentrations used. This result is consistent with placement of the uncompetitive site on the donor side of PS II as suggested in the previous study. In chloride-depleted PS II-enriched membranes azide and fluoride showed similar effects on the S(2) state EPR signals, including a notable increase and narrowing of the g = 4.1 signal. Comparable effects of other anions have been described previously and apparently take place through the chloride-competitive site. The two azide binding sites described here correlate with the results of other studies of Lewis base inhibitors.

Journal Article↗
PubMed2000

Cisplatin-epirubicin-paclitaxel weekly administration with G-CSF support in advanced breast cancer. A Southern Italy Cooperative Oncology Group (SICOG) phase II study.

PURPOSE: It has been shown in vitro that both cisplatin and epirubicin increase the antitumor activity of paclitaxel. Weekly administration could give a substantial improvement in the therapeutic index of cisplatin and paclitaxel. This study was aimed at defining the antitumor activity of a weekly cisplatin-epirubicin-paclitaxel (PET) administration in locally advanced or metastatic breast cancer patients. PATIENTS AND METHODS: Sixty-eight breast cancer patients with advanced disease, who had not received prior chemotherapy (except adjuvant), received weekly cisplatin 30 mg/sqm, paclitaxel 120 mg/sqm and epirubicin 50 mg/sqm plus G-CSF (day 3-5), for a maximum of 12 cycles. Thirty-five patients had stage IIIB and 33 stage IV disease (14 with visceral metastases). RESULTS: All patients were evaluable for response on an intent to treat basis. Overall, 21 complete and 38 partial responses have been recorded for an 87% ORR (95% CI = 76-94%). Fourteen CRs and 19 PRs have been registered in the 35 patients with locally advanced disease for a 94% ORR (95% CI = 81-99%) while 7 CRs and 19 PRs were observed in the 33 patients with metastatic disease for a 79% ORR (95% CI-61-91%). Surgery was performed in 33/35 women with locally advanced disease. Four of these patients (11%) showed no invasive cancer on pathologic examination, and in an additional 8 patients tumor < 1 cm was found in the breast. Only 4/33 patients who underwent surgery relapsed. The projected one-year RFS was greater than 80%. At an 11-month median follow-up (range, 3-19), 11 patients had progressed and 5 had died among the 33 patients with metastatic disease, the median progression-free survival in this group being 14 months. Severe hematologic toxicity was uncommon, grade 3-4 neutropenia and thrombocytopenia occurring in 32% and 4% of patients, respectively. Only 2 episodes of neutropenic sepsis were registered. Packed red blood cell transfusions were required in 7 patients. Vomiting, diarrhoea, mucositis and skin toxicity were severe in 6%, 9%, 10%, and 9% of patients, respectively. Peripheral neuropathy was observed in 47% of patients. CONCLUSIONS: The weekly PET administration is a well tolerated and very effective approach in advanced breast cancer patients. It can produce a 40% clinical complete response rate, with a more than 10% pCR rate in patients with T4 disease, and an about 80% ORR in those with distant metastases. A phase III trial comparing PET with a standard every 3 weeks epirubicin-taxol administration is underway.

Adult↗
PubMed2000

Weekly docetaxel plus gemcitabine or vinorelbine in refractory advanced breast cancer patients: a parallel dose-finding study. Southern Italy Cooperative Oncology Group (SICOG).

PURPOSE: The objective of this study was to determine the docetaxel MTD when combined with gemcitabine or vinorelbine in advanced breast cancer patients who had received previous anthracycline-based chemotherapy for advanced disease. PATIENTS AND METHODS: Advanced breast cancer patients aged between 18 and 70 with ECOG PS 0-2 who had not responded to, or had relapsed after, first-line anthracycline-based chemotherapy, were randomized to receive either gemcitabine 1000 mg/m2 or vinorelbine 25 mg/m2 in combination with escalating doses of docetaxel (starting from 30 mg/m2), all on days 1 and 8 every three weeks. Escalation was stopped if > 33% of patients treated at a given dose level showed DLT at the first cycle. RESULTS: A total of 34 patients with locally advanced (8) or metastatic disease (26) were treated, for a total of 94 cycles delivered. Nineteen patients received docetaxel in combination with gemcitabine and 15 with vinorelbine. All patients had been pretreated with anthracyclines, and 24 of 34 had also received weekly dose-dense paclitaxel. A docetaxel dose of 40/m2 proved to be safe when combined on days 1 and 8 with gemcitabine, while a dose of 35 mg/m2 was tolerated in combination with vinorelbine. Overall, nine episodes of DLT, all of them neutropenia, occurred at the first cycle. Considering all 94 cycles, grades 3 or 4 neutropenia and thrombocytopenia occurred in 15 (44%), and 7 (20%) patients. Non-hematologic toxicity was mild, except for three cases of grade 2 peripheral neuropathy. All patients were assessed for response on an 'intent-to-treat' basis. Overall, five partial responses were recorded (docetaxel + gemcitabine = 3 and docetaxel + vinorelbine = 2), for a 15% (95% CI: 5%-31%) overall response rate. Only 1 of 24 (4%) patients who had received weekly dose-dense paclitaxel responded to treatment. CONCLUSIONS: The weekly docetaxel administration in combination with either gemcitabine or vinorelbine is a well-tolerated treatment for heavily pretreated advanced breast cancer patients. This approach, although sometimes capable of achieving a major response, does not seem advisable in advanced breast cancer patients refractory to both anthracyclines and paclitaxel.

Adult↗
PubMed2000

Recombination of simple molecular ions studied in storage ring: dissociative recombination of H2O+

Dissociative recombination of vibrationally relaxed H2O+ ions with electrons has been studied in the heavy-ion storage ring CRYRING. Absolute cross-sections have been measured for collision energies between 0 eV and 30 eV. The energy dependence of the cross-section below 0.1 eV is found to be much steeper than the E-1 behaviour associated with the dominance of the direct recombination mechanism. Resonant structures found at 4 eV and 11 eV have been attributed to the electron capture to Rydberg states converging to electronically excited ionic states. Complete branching fractions for all dissociation channels have been measured at a collision energy of 0 eV. The dissociation process is dominated by three-body H + H + O breakup that occurs with a branching ratio of 0.71.

Journal Article↗
PubMed2000

Comparative genomic hybridization (CGH) in dogs--application to the study of a canine glial tumour cell line.

Recurrent chromosome aberrations are associated with many human cancers. Detailed cytogenetic analysis of tumors has benefited enormously from the development of molecular cytogenetic techniques based on fluorescence in situ hybridization (FISH). Comparative genomic hybridization (CGH) is a recently developed FISH technique that allows a rapid and comprehensive identification of imbalanced genomic material in tumour DNA. Comparative genomic hybridisation has been used widely in human medicine to evaluate losses and gains of tumour DNA isolated from a variety of sources, including fresh samples, cell-culture material and archival specimens, and has been instrumental in identifying sites in the human genome which contain genies involved in tumour development and progression. This report describes the first application of CGH in the dog, illustrated by the analysis of DNA isolated from a canine glial tumour cell line.

Animals↗
PubMed2000

Developing child abuse prevention, identification, and treatment systems in Eastern Europe.

Although the dissolution of the Soviet Union in 1989 brought a welcome end to the Cold War, the subsequent reestablishment of independent Eastern European countries revealed a host of problems. Among these was frequent child abuse and neglect, although lack of epidemiological data precluded any accurate estimate of prevalence. In an effort to address the problem of child abuse within this rapidly changing sociopolitical environment, the Children's Mental Health Alliance and the Soros Foundation organized the Eastern European Child Abuse and Child Mental Health Project in 1995. The authors describe the development of this multidisciplinary initiative involving collaboration with professionals from 17 countries in Eastern Europe. They highlight the goals, principles, and major phases of the project, as well as some of the challenges involved in its implementation.

Child↗
PubMed2000

A prospective trial of lansoprazole triple therapy for pediatric Helicobacter pylori infection.

BACKGROUND: Triple therapy with a proton-pump inhibitor and two antibiotics is widely used in the treatment of Helicobacter pylori infection in adults. Experience with such therapy in the pediatric population is limited. This was a prospective, nonrandomized, open-label trial to evaluate safety and efficacy of a combination of lansoprazole, clarithromycin, and amoxicillin in symptomatic children with H. pylori infection. METHODS: Children with H. pylori gastritis diagnosed by endoscopy performed for persistent nausea, vomiting, recurrent abdominal pain, and diarrhea with consistent histology were treated with the regimen of 0.45 mg/kg per day lansoprazole divided into two doses (maximum dose, 15 mg twice daily), amoxicillin 40 mg/kg per day in two doses (maximum dose, 1.0 g twice daily), and 250 mg clarithromycin twice daily (<10 years old) or 500 mg twice daily (>10 years old) for 2 weeks. Pre- and posttreatment endoscopic biopsy specimens were graded for the severity of gastritis and H. pylori density by a blinded pathologist. A questionnaire for assessing the severity of symptoms at the time of initial and second endoscopy were completed by patient and/or parent. RESULTS: Thirty-two children (age range, 1-25 years; mean age, 11 years; 19 females, 13 males) were treated with this regimen during an 18-month period. H. pylori organisms with varying grades of gastritis were present in tissue specimens of all patients. Only 28 children had follow-up endoscopy, which showed eradication of H. pylori in 15 (54%) children. Histologic symptoms of gastritis improved after therapy in the whole group. Overall, symptoms of vomiting, abdominal pain, diarrhea, anorexia, and halitosis significantly improved (P < 0.05). Minor adverse effects of therapy occurred in 25% of patients. CONCLUSIONS: Symptoms, histologic, and endoscopic findings improved after triple therapy in children with H. pylori gastritis; however, eradication of bacteria was achieved in only 56% of children.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Fludarabine induced intestinal pseudo-obstruction: case report and literature review.

Intestinal pseudo-obstruction is a recognized but rare complication of chemotherapy. Vinca alkaloids and cytarabine have been reported to be associated with intestinal pseudo-obstruction. We report a case of fludarabine induced severe intestinal pseudo-obstruction in a 66-year-old man suffering from non-Hodgkin's lymphoma, and describe our successful management of this with a combination of parasympathomimetic and mechanical decompression, after failure of conservative management.

Aged↗