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Biomedical subjects

C Thomas

Publications and source records attributed to C Thomas.

At least 271 records · Page 15Linked to original sources

The hydrolysis product of ICRF-187 promotes iron-catalysed hydroxyl radical production via the Fenton reaction.

d-1,2-Bis(3,5-dioxopiperazine-1-yl)propane (ICRF-187) (ADR-529) is a drug that ameliorates the cardiotoxicity of Adriamycin. The drug enters cells where hydrolysis leads to its diacid diamide product, dl-N,N'-dicarboxamidomethyl-N,N'-dicarboxymethyl-1,2-diamino propane (ICRF-198) (ADR-925), which is structurally similar to ethylenediaminetetraacetic acid (EDTA). The protective mechanism of ICRF-187 is unknown, but a plausible explanation is that ICRF-198 chelates iron intracellularly to prevent iron-dependent free radical reactions such as hydroxyl radical (.OH) production. We have compared Fe(ICRF-198) with Fe(EDTA) in its ability to promote .OH formation in several Fenton reaction systems. The Fenton reaction was studied with H2O2 and Fe2+ chelates or catalytic amounts of the iron chelates in the presence of Adriamycin radicals, paraquat radicals, superoxide anion radicals (O2-), and ascorbate as reducing species. .OH was detected with deoxyribose and dimethyl sulfoxide. The two methods gave comparable results. Fe(ICRF-198) was 80-100% as effective as Fe(EDTA) at promoting .OH production in the presence of the organic radicals and ascorbate, 30-70% in the presence of O2-, and 150% with non-cycling Fe2+. Fe(EDTA) is a more efficient catalyst of .OH production than physiological chelates such as ADP, ATP and citrate. Therefore, by comparing previous work which examined physiological chelates and Fe(EDTA) with the present work, Fe(ICRF-198) appears to be a better .OH catalyst than the physiological chelates. These results suggest that ICRF-198 generated in vivo from ICRF-187 would not protect against intracellular .OH production. They also imply that .OH production may not be as important in Adriamycin cardiotoxicity as other radical reactions, such as lipid peroxidation and thiol oxidation, that are inhibited by ICRF-198.

Ascorbic Acid↗

Interactive video conferencing: a means of providing interim care to Parkinson's disease patients.

Inequity in health care delivery is attributable to a variety of factors including geographic isolation. Patients living far from major urban centers have limited access to medical specialists. In the instance of Parkinson's disease (PD), optimal assessment and care may depend upon availability of specialty health care providers. In order to broaden health care access, interactive video conference (IVC) units are being developed for medical use. IVC allows a patient at a distant site to be "seen and heard" by a hospital-based physician; simultaneously, the patient can "see and hear" the doctor. To establish the validity of this technology in the evaluation of PD, nine patients were independently examined and scored (UPDRS) by two movement disorder specialists. One examination was performed in-person by the usual physician. The other examination was performed on the same day via IVC over a distance of 350 miles by an examiner previously unfamiliar with the patients. Individual patient scores did not differ based on examiner (Spearman Rho Correlation Coefficients: UPDRS total scores r = 0.933, p < 0.0002; Hoehn and Yahr Scale r = 0.883, p < 0.001). A standardized exit interview was conducted to assess patients' perceptions of this application of video technology. Responses were favorable and virtually all patients viewed this as a means of accessing better health care. We conclude that valid motor assessments of PD patients can be made via IVC.

Aged↗

Human bradykinin B2 receptor: nucleotide sequence analysis and assignment to chromosome 14.

Functional cDNA clones for human bradykinin B2 receptor were isolated from uterus RNA by a polymerase chain reaction (PCR)-based method and by screening a human cosmid library with rat bradykinin B2 receptor probe. We isolated several overlapping clones from the cosmid library, each of which encodes the entire protein coding sequence. The human bradykinin B2 receptor gene codes for a 364-amino-acid protein with a molecular mass of 41,442 Da that is highly homologous to rat bradykinin B2 receptor cDNA (81%). The entire human cDNA sequence was cloned into an expression vector and mRNA was synthesised by in vitro transcription. Applications of bradykinin caused membrane current responses in Xenopus oocytes injected with the in vitro-synthesized mRNA. Preincubation with the potent B2 antagonist, HOE140, prevented this response. The genomic clone is intronless, and we have identified an upstream promoter region and a downstream polyadenylation signal. The human bradykinin B2 receptor gene has been mapped to chromosome 14 using PCR to specifically amplify DNA from somatic cell hybrids.

Amino Acid Sequence↗

The coordination of posture and voluntary movement in patients with hemiparesis.

Postural adjustments associated with the task of raising oneself on tiptoes were investigated in a reaction time paradigm in six normal subjects and six patients with hemiparesis due to stroke. Body and ankle position in space were measured by means of a movement analysis system (ELITE). The findings indicate that the task of going up on tiptoes is performed in two steps. First, the centre of gravity is shifted forward to a position perpendicular to the forefoot. This movement is initiated by a phasic burst of EMG activity in the tibialis anterior (TA). The activity of the quadriceps femoris (QUA) aids the forward shift and together with the biceps femoris (BF) stabilizes the knee. Following these postural adjustments, the action of going up on tip-toes is performed mainly by the gastrocnemius medialis (MG). The basic pattern of preparatory (TA, QUA, BF) and focal (MG) activity was disturbed in its temporal sequence in patients with hemiparesis. The analysis of the biomechanical data showed smaller movement velocities for leaning forward and going up on tiptoes in patients, with increased movement amplitude on the paretic side. In addition, the correlation between the start of horizontal (leaning forward) and vertical (going up on tiptoes) hip movement was lost in patients. The preserved correlation between the latency of MG activity and the onset of the vertical hip movement on the paretic side in patients and the loss of correlation on the non-paretic side indicates that the EMG activity on the healthy side is adapted to the functional requirements of the affected side.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evidence for developmentally based diagnoses of oppositional defiant disorder and conduct disorder.

This paper compares the validity of DSM-III-R diagnoses of oppositional defiant disorder (ODD) and conduct disorder (CD) and an alternative option which is subdivided into three levels according to developmental sequence and severity: modified oppositional disorder (MODD), intermediate CD (ICD), and advanced CD (ACD). Using a sample of 177 boys followed over 3 years, both the DSM-III-R and the alternative diagnostic constructs are evaluated on three criteria: symptom discriminative validity, and diagnostic external and predictive validity. Most DSM-III-R ODD and CD symptoms discriminated between ODD and CD, but exceptions are noted. Additional analyses demonstrated considerable overlap among DSM-III-R oppositional symptoms. The majority of the symptoms proposed for the alternative option could be assigned to a specific level based on acceptable symptom discrimination. External validity lent support to the distinctions between DSM-III-R ODD and CD, and between MODD, ICD, and ACD. MODD was a better predictor than ODD of which MODD, ICD, and ACD. MODD was a better predictor than ODD of which boys received a later diagnosis of CD. Suggestions are made for the inclusion and exclusion of symptoms for developmentally based diagnoses of oppositional and conduct disorders.

Antisocial Personality Disorder↗

Radiosensitivity, blood perfusion and tumour oxygenation after perflubron emulsion injection.

The effect of 90% and/or 100% w/v perflubron (perfluorooctyl bromide (PFOB); Alliance Pharmaceutical Corp.) emulsions on radiosensitivity, tumour relative perfusion and oxygenation was studied using EMT6 tumours in nude mice. Perflubron (2-15 ml/kg) emulsion was injected. The mice inhaled carbogen for 30 min and 60 min prior to irradiation. The radiosensitizing effect of the 90% w/v emulsion was maximal at 4 ml/kg. The tumour relative perfusion diminished after injection of both 100% and 90% w/v emulsions in carbogen-breathing mice at a dose of 15 ml/kg. This drop could explain the lack of efficiency of these treatments at this high concentration. Lastly, tumour oxygenation was increased after administration of perflubron emulsion plus carbogen.

Animals↗

Hemodynamics in subclavian-steal syndrome: difficulties in their evaluation.

In a patient with subclavian-steal syndrome transcranial Doppler sonography detected transient retrograde basilar blood flow whereas routine angiography failed to document this condition. Thus, orthograde basilar blood flow at routine angiography does not rule out basilar steal. Presumably the forced injection of contrast media conceals less pronounced steal phenomena. Our exemplary case indicates that a subgroup of patients with vertebro-basilar symptoms concomitant with basilar flow abnormalities may benefit from invasive or semi-invasive treatment.

Angiography↗

Sympathetic activity enhances glucose-related ischemic injury in the rat.

BACKGROUND: Studies have shown that increased sympathetic activity or increased blood and brain glucose concentration worsen postischemic brain damage. The authors evaluated the interaction of plasma glucose with epinephrine and norepinephrine during incomplete cerebral ischemia in the rat using ganglionic blockade. METHODS: Rats were anesthetized with 25 micrograms.kg-1.h-1 fentanyl and 70% nitrous oxide in oxygen. Ganglionic blockade was produced in 30 rats using 8 mg/kg hexamethonium intravenously. Three plasma glucose ranges, low < 150 mg/dl, moderate = 150-300 mg/dl, and high > 300 mg/dl, were produced in each group. Ischemia was induced by unilateral carotid ligation and hemorrhagic hypotension to 30 mmHg for 30 min. Plasma norepinephrine and epinephrine were measured by radioimmunoassay. Neurologic outcome was evaluated daily for 3 days after ischemia. RESULTS: Ganglionic blockade decreased blood pressure before the start of ischemia and plasma epinephrine and norepinephrine during ischemia (P < 0.05). Neurologic outcome was significantly worse in rats with high glucose compared with low glucose concentrations with and without ganglionic blockade (P < 0.05). Neurologic outcome and stroke-related mortality were worse in rats with increased plasma epinephrine and norepinephrine compared with rats with ganglionic blockade when plasma glucose was less than 300 mg/dl (P < 0.05). CONCLUSIONS: These results indicate that increased concentration of catecholamines enhance glucose-related injury during incomplete ischemia in rats.

Animals↗

[Urinary bladder nuclear cytology: results of karyometric investigations].

To assess the value of nuclear morphometry in the cytological diagnosis of urinary bladder carcinoma, washouts of the urinary bladder from 168 patients with histological established bladder cancer were studied. Morphometrical measurements were done on the nuclei of the exfoliated cells. This retrospective study showed that the nuclear parameter obtained by automated image analysis may be helpful in the differential diagnosis between neoplastic and non-neoplastic urinary bladder disease and correlate fairly with the classic histologic grading of malignancy in transitional cell carcinoma of the urinary bladder.

Cell Nucleus↗

[Use of fluorine-19 nuclear resonance spectroscopy for the measurement of changes induced in blood perfusion volume in experimental tumors in vivo].

The biological response of some anti-cancer therapeutic agents is probably mediated via the tumour vasculature. A novel approach using 19F NMR spectroscopy in vivo has been developed to directly measure changes in vascular perfusion volume in experimental tumours. A 100% w/v perfluorooctylebromide (PFOB) emulsion was used as a tracer. For a fixed position of a 7 mm surface coil placed over the tumour, the signal from the PFOB rapidly reached an equilibrium value remaining unchanged for at least 2 hours. Since the strength of the fluorine signal is directly proportional to the perfusion volume of the tumour vasculature, reduction of signal intensity should correspond directly to any reduction in volume which may be a manifestation of a change in the tumour blood flow. This hypothesis was investigated using hydralazine as a physiological modifier of tumour blood flow. Administration of 5 mg/kg of hydralazine following dosing with the PFOB emulsion reduced the 19F signal intensity from the murine tumors RIF-1 and KHT and from the human tumour HT29 with no or little reduction in the SCCVII/Ha murine and HX118 human tumours. Changes in blood volume in KHT tumour accompanied local changes in tumour blood flow rate as measured by the Xe-133 clearance rate technique. Thus, these data demonstrate the potential of the PFOB emulsion as a 19F NMR tracer of the vasculature to measure changes induced by therapeutic agents on blood volume in accessible tumours. This method may also be useful to detect early changes in blood volume produced during angiogenesis of solid tumours or angiostatic activity of anti-cancer drugs.

Animals↗

[An uncommon site of malignant germ cell tumor secreting alpha fetoprotein: the posterior mediastinum].

BACKGROUND: While germ cell tumors generally occur in the gonads, they may also appear at other sites, from the sacrococcygeum area to the central nervous system. This report describes a case of such a tumor in the posterior mediastinum that developed intraspinally in a dumb-bell fashion. CASE REPORT: A 2 1/2 year-old girl was admitted for abdominal tenderness, gait disturbance and fever. Clinical examination showed spastic paraparesis and bladder dysfunction. Thoracic X-rays showed a left postero-superior mediastinal mass with rib erosion. MRI showed that this mass had developed intraspinally between the intervertebral foramina and caused spinal cord compression at T4, T5, T6. The tumor was not calcified. Surgical resection via laminectomy was performed in emergency, but the T5 root had to be excised. Pathologic examination showed histologic features of yolk sac carcinoma; the serum alpha-foetoprotein was elevated (12, 400 IU/ml). The patient was given chemotherapy for 6 months and is well 2 years later. CONCLUSION: Germ cell tumors may appear in unusual sites. They can be identified by measuring biological markers, and this avoid primary surgery.

Child, Preschool↗

Liver metastasis model of colon cancer in the rat: immunohistochemical characterization.

Inoculation of 3 x 10(4) to 3 x 10(5) CC531 colon adenocarcinoma cells into the portal vein of syngeneic WAG/Rij rats provides a reproducible animal model of colon cancer liver metastasis with macroscopically visible tumor nodules at day 25 after inoculation. In this study, the inflammatory cell response in the liver sinusoids against locally induced metastases was also investigated using immunohistochemical methods. Host immune reactive cells accumulated in the liver sinusoids of tumor-bearing livers, especially resident Kupffer cells (KC; ED1+/ED2+), and to a lesser extent pit cells (OX8+/0X19-), T lymphocytes (OX8+/OX19+) and polymorphonuclear leukocytes (PMN; HIS48+). All these cell types may be involved in the lysis of CC531 cells in the liver, although only major histocompatibility complex class II+ monocytes (3D11+/ED1+/ED2-), but not resident KC, T lymphocytes nor PMN, accumulated at the peritumoral area between liver parenchyma and tumor foci. Especially monocytes but also PMN, lymphocytes and pit cells appeared to infiltrate the stromal tumor compartment. In view of the low cell dose needed, the rat liver metastasis model of colon cancer used in this study reflects well the human, weakly immunogenic, tumor-host relationships and provides an excellent opportunity for the study of cellular reactions related to chemo- and/or immunotherapy protocols.

Adenocarcinoma↗

The antinuclear antibody test. When is a positive result clinically relevant?

The antinuclear antibody (ANA) test is sensitive but not specific. Many nonrheumatic diseases and conditions can cause positive results, and some healthy persons have positive results. ANA testing should not be used to evaluate patients who have vague complaints or symptoms. Rather, it is best used in patients with signs or symptoms of rheumatic disease to justify further specific investigation aimed at confirming a diagnosis.

Age Factors↗

[Evaluation of ambulatory anesthesia at CHU, Brest].

Outpatient anaesthesia was investigated for a two-month period by means of a questionnaire filled from the preoperative anaesthesia consultation to the surgical procedure and the discharge of the patient. 868 consultations led to schedule 260 ambulatory procedures. ENT (88 patients), paediatric surgery (73 patients) and gynaecology (63 patients) were most frequently concerned. Indications of ambulatory practice could probably be enlarged provided that recovery rooms and surgical schedules were fully adapted.

Adolescent↗