Showing papers by "St Thomas' Hospital published in 1994"
TL;DR: A working party of 13 dermatologists, two family practitioners and a paediatrician was assembled, with the aim of developing a minimum list of reliable discriminators for atopic dermatitis, finding that the discriminatory value of these criteria was satisfactory when tested against a further sample of 150 patients drawn from the community, who did not have skin disease.
Abstract: A working party of 13 dermatologists, two family practitioners and a paediatrician was assembled, with the aim of developing a minimum list of reliable discriminators for atopic dermatitis. Each physician was asked to select 10 consecutive new cases of unequivocal mild to moderate atopic dermatitis and 10 controls with other inflammatory dermatoses. Each subject was examined by two independent observers, who were blind to the clinical diagnosis and study aim, with regard to 31 clinically useful diagnostic features for atopic dermatitis. Two hundred and twenty-four patients were studied (120 cases and 102 controls). Using the key physician's clinical diagnosis as a gold standard, the sensitivity and specificity of each of the 31 diagnostic criteria were tested. Using multiple logistic regression techniques, a minimum set of diagnostic criteria for atopic dermatitis was derived. These were: history of flexural involvement, history of a dry skin, onset under the age of 2, personal history of asthma, history of a pruritic skin condition, and visible flexural dermatitis. Adjustment for age, sex, region, social class and ethnic group did not alter the choice of final criteria. The discriminatory value of these criteria was also satisfactory when tested against a further sample of 150 patients drawn from the community, who did not have skin disease.
1,051 citations
TL;DR: These two independent validation studies suggest that the newly proposed criteria for atopic dermatitis perform reasonably well in hospital out‐patient patients and further validation in community settings and in developing countries is needed.
Abstract: In order to qualify as a case of atopic dermatitis, we propose that an individual must have an itchy skin condition plus three or more of the following: history of flexural involvement, a history of asthma/hay fever, a history of a generalized dry skin, onset of rash under the age of 2 years, or visible flexural dermatitis. When tested in an independent sample of 200 consecutive dermatology outpatients of all ages, this arrangement of the diagnostic criteria achieved 69% sensitivity and 96% specificity when validated against physician's diagnosis. Based on the findings of this first exercise, minor modifications in the wording of the criteria were undertaken, and these were tested on a sample of 114 consecutive children attending out-patient paediatric dermatology clinics. Overall discrimination improved, with a sensitivity of 85% and specificity of 96%. The simplified criteria are easy to use, take under 2 min per patient to ascertain, and do not require subjects to undress. These two independent validation studies suggest that the newly proposed criteria for atopic dermatitis perform reasonably well in hospital out-patient patients. Further validation in community settings and in developing countries is needed.
826 citations
TL;DR: The results indicate that NGF and NT-3 act on functionally distinct populations of adult sensory neurons and suggest that a sizeable number of small DRG neurons may not respond to neurotrophins via a known Trk in the adult rat.
580 citations
TL;DR: The glyoxalase system was characterized in blood samples from patients with insulin-dependent diabetes mellitus, patients with non-insulin-dependent Diabetes mellitus and 21 normal healthy control subjects.
Abstract: 1. The metabolism of methylglyoxal by the glyoxalase system may be linked to the development of diabetic complications. The glyoxalase system was characterized in blood samples from patients with insulin-dependent diabetes mellitus (n = 43), patients with non-insulin-dependent diabetes mellitus (n = 107) and 21 normal healthy control subjects. 2. The concentrations of glyoxalase metabolites, methylglyoxal, S-D-lactoylglutathione and D-lactate, were increased in diabetic patients, relative to normal control subjects: methylglyoxal [median, range (n) pmol/g], insulin-dependent patients, 470.7, 85.6-1044.3 (42), P 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
556 citations
TL;DR: It is concluded that GH deficiency in adults is most reliably identified by stimulatory testing, and that IGF-I and IGFBP-3 are poor diagnostic tests of adult GH deficiency.
485 citations
TL;DR: Patients with APs plus SLE and PAPS have similar clinical profiles, although heart valve disease, hemolytic anemia, low C4 levels, and neutropenia seem to be more common in patients with APSplus SLE.
446 citations
Journal Article•
TL;DR: It is reported here that the number of recently established lung metastases of B16 melanoma in C57BL mice treated with ganciclovir is reduced compared to controls after multiple i.v. administrations of high titer retroviral supernatant encoding the HSVtk gene, but not after administration of liposome-complexed plasmid DNA.
Abstract: Previously we have demonstrated safe and effective transfer of the HSVtk cytotoxic gene to primary murine melanoma tumors by direct injection of plasmid and retroviral vectors in which the HSVtk gene is driven by the tissue-specific tyrosinase promoter. However, for general clinical application such forms of therapy should, ideally, be effective against disseminated metastases. We report here that the number of recently established lung metastases of B16 melanoma in C57BL mice treated with ganciclovir is reduced compared to controls after multiple i.v. administrations of high titer retroviral supernatant encoding the HSVtk gene, but not after administration of liposome-complexed plasmid DNA. Using polymerase chain reaction analysis, integration of the provirus was observed in metastasis-bearing lungs (4 of 6 mice) and in the spleens of some ganciclovir-treated animals (2 of 6 mice) but not in the testes, brain, heart, liver, or kidney. The reduction in the number of experimental metastases in C57BL mice exceeded the anticipated extent of transduction of tumor cells, which is indicative of a marked bystander effect. This magnitude of reduction was not observed in immunodeficient athymic mice, suggesting that the immune system plays some part in the bystander effect. In support of these data, we show that, whereas the parental tumor cells are only poorly immunogenic, an effective antitumor immune response is generated following the killing of neoplastic cells in vivo as a result of treatment with ganciclovir. These effects may be responsible for augmenting the efficacy of retroviral infection. The combination of local cell killing by the HSVtk/ganciclovir system and the induction of antitumor immunity suggests new opportunities for the design of vectors for the gene therapy of cancer.
352 citations
Journal Article•
TL;DR: In this paper, a PET scan was performed using 18F-fluorodeoxyglucose (FDG) in two patients with hilar lymphadenopathy in whom the clinical differential diagnosis was between sarcoidosis and lymphoma.
Abstract: Whole-body PET scanning was performed using 18F-fluorodeoxyglucose (FDG) in two patients with hilar lymphadenopathy in whom the clinical differential diagnosis was between sarcoidosis and lymphoma. Both patients were later proven to have sarcoidosis. Uptake of 18FDG was seen in both intra- and extrathoracic lesions as well as in associated erythema nodosum. One patient underwent a repeat scan after steroid therapy where a marked decrease in hilar uptake was seen. Fluorine-18-fluorodeoxyglucose uptake is observed in lymph nodes with sarcoid involvement. Further investigation is necessary to assess if quantitative differences exist between sarcoid and malignant lymphadenopathy.
301 citations
TL;DR: Adding small doses of CZP with simultaneous reduction of VPA was the most effective and better tolerated form of medication, particularly in patients demonstrating an adverse reaction or requiring a large VPA dosage.
Abstract: Summary: We made a long term prospective study of 66 patients with juvenile myoclonic epilepsy (JME). Prevalence was 10.2% among 672 patients with epilepsies. Sex distribution was equal. Sixty-three were not diagnosed on referral; JME was not initially recognized in the epilepsy clinic in 22. Clinical typical absence seizures were reported in 33.3%, myoclonic jerks in 97% and generalized tonic-clonic seizures (GTC) in 78.8% of the patients. Mean age (±SD) at onset was 10.5 ± 3.4 years (range 5–16 years) for absence seizures, 15 ± 3.5 years (range 8–26 years) for myoclonic jerks, and 16 ± 3.5 years (9–28) for GTC. Absence predated myoclonic jerks by 3.9 ± 2.3 years (range-1–9 years) and GTC by 4.4 ± 2.7 years (range 1–8 years) in 14 (21.2%) patients who manifested all three types of seizure. Absence were never antedated by myoclonic jerks or GTC. Myoclonic jerks occurred on awakening in 87.5% of the patients. GTC occurred mainly on awakening, but other patients had nocturnal or diurnal GTC with no circadian distribution. Neurologic examination was normal for all patients except for tremor of the hands similar to essential tremor, noted in 35% of patients. Computed tomography (CT) brain scans were normal: 93% of patients had precipitating factors: sleep deprivation (89.5%), fatigue (73.7%), photosensitivity (36.8%; television and video games 8.8%), menstruation (24.1% of women), mental concentration (22.8%), and stress (12.3%). Incidence of JME among siblings (13 of 41 examined families) implies an autosomal recessive mode of inheritance for this Arab population. EEGs were frequently normal in treated patients. At least one abnormal EEG was recorded in 56 (84.9%) patients. Abnormalities consisted mainly of generalized discharges of spike/double spike and/or polyspike and slow wave. Frequent multiple spikes and discharge fragmentations varied from 0.5to 20-s duration (mean 6.8 s). Twenty (30.3%) had focal abnormalities, and 18 (27.3%) had photoconvulsive discharges. Eighty-eight percent of patients remained seizure-free for 3 years of follow-up. Effective treatment was achieved with valproate (VPA); control of myoclonic jerks was improved with clonazepam (CZP). CZP monotherapy did not consistently prevent GTC. Adding small doses of CZP with simultaneous reduction of VPA was the most effective and better tolerated form of medication, particularly in patients demonstrating an adverse reaction or requiring a large VPA dosage. VPA dosage was successfully reduced in 15 patients who were seizure-free for >2 years and had infrequent seizures before treatment, but 9 of 11 patients relapsed after VPA discontinuation.
ReSUMe
Les auteurs ont entrepris une etude prospective a long terme de 66 patients presentant une epilepsie myoclonique juvenile (EMJ). La prevalence etait de 10.2% parmi 672 patients presentant une epilepsie. La distribution entre les sexes etait egale. Soixante trois patients n'etaient pas diagnostiques au moment de leur premier contact; l'epilepsie myoclonique juvenile n'avait pas ete reconnue initialement dans la consultation epileptologique chez 22 patients. Les absences cliniques etaient reporetes chez 33.3%, des secousses myocloniques chez 97% et des crises tonico-cloniques chez 78.8% des patients. L'âge moyen du debut etait de 10.5 ± 3.4 ans (±SD, limite 5 a 16) pour les absences, 15 ± 3.5 (8 a 26) pour les secousses myocloniques et 16 ± 3.5 (9 a 28) pour les crises generalisees tonico-cloniques. Les absences precedaient les myoclonies de 3.4 ± 2.3 annees (de 1 a 9) et les crises generalisees tonico-cloniques de 4.4 ± 2.7 annees (1 a 8) chez les 14 patients (21.2%) qui presentaient les trois types de crises. Les absences n'ont jamais ete precedees par des secousses myocloniques ou par des crises generalisees tonicocloniques. Les secousses myocloniques etaient constatees au reveil chez 87.5% des patients. Les crises generalisees tonicocloniques survenaient principalement au reveil, mais d'autres patients avaient des crises nocturnes ou diurnes sans distribution circadienne. L'examen neurologique etait normal chez tous les patients, en dehors d'un tremblement des mains semblable au tremblement essentiel, constatt chez 35% des patients. Les scanners cerebraux ont toujours ete normaux. Les facteurs declenchant des crises ont ete constates chez 93% des patients: privation de sommeil chez 89.5%, fatigue chez 73.7%, photosensibilite chez 36.8% (television et jeux video 8.8%), menstruation chez 24.1% des femmes, concentration mentale chez 22.8%, stress chez 12.3%. L'incidence de l'EMJ dans les fratries (13 des 41 familles examinees) implique un mode de transmission autosomique recessif dans cette population d'origine arabe. Les EEG etaient souvent normaux chez les patients traites. Au moins un EEG anormal a ete enregistre chez 56 patients (84.9%). Les anomalies ttaient representtes surtout par des decharges generalisees de pointes, doubles pointes ou poly pointes-ondes lentes. La duree des pointes multiples et des fragmentations des decharges variaient de 0.5 a 20 secondes (en moyenne 6,8 secondes). Les anomalies focales ont ete constatees chez 20 patients (30.3%) et des decharges photoconvulsives chez 18 patients (27.3%). Quatre vingthuit pour cent des patients sont restes sans crise pendant 3 ans ou plus de suivi. Le traitement efficace a utilise le valproate (VPA). Le controle des secousses myocloniques a ete ameliore avec le clonazepam (CZP). Une monotherapie par CZP n'a pas permis de prevenir de facon constante les crises generalisees tonico-clonique. Une substitution partielle utilisant le valproate, avec de petites doses de CZP, a ete le traitement le plus efficace et le mieux tolere, particulierement chez les patients presentant des effets secondaires ou necessitant de fortes doses de VPA. La dose de VPA a ete reduite avec succes chez 14 patients qui n'avaient plus de crises depuis plus de 2 ans et qui n'avaient que de rares crises avant le traitement. Cependant, 9 patients sur 11 ont recidive aprts l'arret du VPA.
RESUMEN
Los autores han llevado a cabo un estudio prospectivo a largo plazo de 66 enfermos con Epilepsia Mioclonica Juvenil (JME). La prevalencia fue de 10.2% en 672 casos con epilepsia. La distribucion entre sexos fue equivalente. Sesenta y tres casos no habian sido diagnosticados por quienes enviaban los enfermos y la JME no fue reconocida inicialmente en la clinica de epilepsia en 22 sujetos. Los tipicos ataques de ausencia clinica aparecieron en 33.3%, los movimientos mioclonicos en 97% y los ataques generalizados tonico-clonicos (GTCs) en 78.8% de los enfermos. La edad media (tSD)a1 comienzo fue de 10.5 ± 3.4 (rango 5–16) ahos para las ausencias, 15 ± 3.5 (8–26) para los movimientos mioclonicos y 16 ± 3.5 (9–28) para los GTCs. Las ausencias precedieron a los movimientos mioclonicos en 3.4 ± 2.3 anos (rango 1–9) y en 4.4 ± 2.7 a los GTCs (rango 1–8) y en 14 anos (21.2%) en enfermos que presentaban los tres tipos de ataques. Las ausencias nunca fueron precedidas de ataques mioclonicos o GTCs. Las mioclonias se presentaron durante la vigilia en 87.5% de los enfermos. Los GTCs predominaron durante la vigilia pero otros enfermos tenian GTCs nocturnos o diurnos sin distribucion circadiana. La exploracidn neurologica fue normal en todos los pacientes con la excepcion de temblor en las manos semejante al temblor esencial que aparecio en el 35% de los enfermos. El CT de cerebro fue normal. En el 93% de los enfermos se encontraron factores precipitantes: la deprivacion del suedo en 89.5%, la fatiga en 73.7%, la fotosensibilidad en 36.8% (television y juegos de video en 8.8%), la menstruation en el 24.1% de las mujeres, el retraso mental en el 22.8% y el stress en el 12.3%. La incidencia de los JME entre hermanos (13 en 41 de las familias examinadas) sugiere un modo autosomico recesivo de herencia para esta poblacion Qrabe. Los EEGs fueron frecuentemente normales en los enfermos tratados. A1 menos un EEG anormal fue registrado en 56 enfermos (84.9%). Las anomalias consistieron, generalmente, en descargas generalizadas de puntddoble punta ylo polipuntas y ondas lentas. La frecuencia de las mliltiples puntas y la fragmentacion de las descargas variaron de 0.5–20 s (promedio 6.8 s) de duracion. Las anomalias focales se observaron en 20 (30.3%) y las descargas fotoconvulsivas en 18(27.3%) pacientes. El 88% de los enfermos permanecieron libres de ataques durante 3 o mas anos de seguimiento. La eficacia del tratamiento se consiguio con valproato (VPA) que controlo los movimientos mioclonicos y mejoro con clonazepam (CZP). La monoterapia con CZP no evito de mod0 consistente las GTCs. La sustitucion parcial de VPA por dosis bajas de CZP fue la medicacion mas eficaz y mejor tolerada particularmente en enfermos que demostraban reacciones adversas o requerian dosis altas de VPA. La reduccibn de las dosis de VPA fue posible en 14 enfermos que estaban libres de ataques durante mas de 2 afios y habian tenido ataques infrecuentes antes del tratamiento. Sin embargo 9 de 11 pacientes volvieron a tener episodios a1 interrumpir el VPA.
299 citations
TL;DR: These natural history data provide a useful estimate for planning therapeutic intervention trials and identify the major factors that influence this rate of contralateral knee OA in middle aged women in the general population with existing unilateral disease.
Abstract: OBJECTIVES--The natural history of knee osteoarthritis (OA) is poorly understood. The principal aim was to assess the rate of contralateral knee OA in middle aged women in the general population with existing unilateral disease and to identify the major factors that influence this rate. METHODS--Fifty eight women aged (45-64) from a general population study cohort were identified with unilateral knee OA diagnosed radiologically (Kellgren and Lawrence 2+) (K&L). Follow up AP films were obtained at 24 months and compared with the baseline for K&L grade and individual features of osteophytes and joint space. RESULTS--Twenty women (34%) developed incident disease in the contralateral knee (based on K&L 2+ or osteophyte changes) and 22.4% (n = 13) of women progressed radiologically in the index joint. Obesity at baseline was the most important factor related to incident disease, 47% of women in the top BMI tertile developed OA, compared with 10% in the lowest tertile: relative risk 4.69 (063-34.75). No clear effect was seen for age, physical activity, trauma or presence of hand OA. CONCLUSIONS--Over one third of middle aged women with unilateral disease will progress to bilateral knee OA within two years and a fifth will progress in the index joint. Obesity is a strong and important risk factor in the primary and secondary prevention of OA. These natural history data provide a useful estimate for planning therapeutic intervention trials.
295 citations
TL;DR: The results suggest that dedifferentiated liposarcomas, as a subgroup among the “MFH-like” sarcoma, have a better prognosis than pleomorphic sarcomas as a whole.
Abstract: Dedifferentiated liposarcoma is uncommon, and only a small number of cases have been documented. We describe the clinicopathologic features in a series of 32 cases. All patients were adults (age range, 37-83 years; median, 67 years); 20 were men and 12 were women. Commonest site was the retroperitoneum (fifteen cases); six cases arose in the limbs, four in the paratesticular region, three in the peritoneal cavity, two on the trunk, and one each in the buttock and larynx. One primary tumor was subcutaneous. Thirty tumors arose de novo (i.e., combined with well-differentiated tumor in the primary lesion), while two developed in recurrences of a previously well-differentiated liposarcoma. The well-differentiated component was most often lipoma-like and typically there was a histologically abrupt transition to spindle celled nonlipogenic tumor. The dedifferentiated component most often resembled either storiform "malignant fibrous histiocytoma" ("MFH") with limited pleomorphism or myxofibrosarcoma (myxoid "MFH"); the latter pattern is rarely otherwise seen in the retroperitoneum. A small number of cases showed appearances reminiscent of myxoid embryonal rhabdomyosarcoma. An unusual feature in three cases was the occurrence of a discontinuous micronodular pattern of dedifferentiation. Average follow-up of 5.6 years (range, 3 months to 33 years) in 27 cases have revealed local recurrence in 14 patients and systemic metastases in only four patients. The primary sites of the metastasising cases were upper back, thigh, retroperitoneum, and paratesticular region. There have been only seven tumor-related deaths. Good prognosis in de novo dedifferentiated liposarcomas seems unrelated to the extent or morphologic pattern of dedifferentiation. However, high mitotic activity in the dedifferentiated component was associated with a more aggressive clinical course. Our study underlines that dedifferentiation in peripherally located or even subcutaneous liposarcomas does occur, albeit rarely, and that dedifferentiated liposarcomas of the limbs may metastasize. The results suggest that dedifferentiated liposarcomas, as a subgroup among the "MFH-like" sarcomas, have a better prognosis than pleomorphic sarcomas as a whole.
TL;DR: It is hoped that the results of various controlled therapeutic trials in the APS will indicate better ways of managing these difficult manifestations and the pathogenesis and the optimal management of the syndrome are uncertain.
Abstract: ConclusionConfirmatory evidence that aPL (the LA or aCL) are associated with an increased risk for arterial and venous thrombosis, recurrent spontaneous abortions, and fetal loss has led to increased laboratory requests for identification of these antibodies. Criteria for the definition of the APS is now well established. At present both the pathogenesis and the optimal management of the syndrome are uncertain. Treatment directed against the secondary thrombotic event is proving more successful than that directed against the underlying immunological abnormality. It is hoped that the results of various controlled therapeutic trials in the APS will indicate better ways of managing these difficult manifestations.
TL;DR: The results suggest that the oligopeptide corresponding to aminoacids 31-49 of A-gliadin is toxic in vivo, but there is no evidence of toxicity of the far N-terminal peptide, residues 3-21, which may contain an epitope to which patients with coeliac disease display variable sensitivity.
TL;DR: Within‐observer variation for the recording of physical signs was substantially better than between‐ob Server variation, and some signs showed poor agreement, such as keratosis pilaris, xerosis, orbital pigmentation, fine hair, and extensor dermatitis.
Abstract: The level of agreement between 14 physicians as to what constitutes a case of atopic dermatitis was tested on 15 selected patients with a range of diagnoses. Between-observer agreement was good, with a mean pair agreement index (P0) of 0.94, and a chance corrected index (kappa) of 0.78. Between-observer agreement in the recording of 18 separate physical signs of atopic dermatitis was then tested by asking the 14 physicians to note the presence or absence of each sign in a different group of patients to those seen in the first part of the exercise. Substantial between-observer agreement (kappa > 0.61) was only present for truncal dermatitis. Most signs showed only fair to moderate agreement (kappa 0.21-0.60), and some signs, such as keratosis pilaris, xerosis, orbital pigmentation, fine hair, and extensor dermatitis, showed poor agreement (kappa 0.01-0.20). The findings were similar when the responses of two independent observers from the national study outlined in Paper I were compared for each sign. Within-observer variation for the recording of physical signs was substantially better than between-observer variation. Physicians interested in atopic dermatitis agree reasonably well on what constitutes a typical case of atopic dermatitis. Between-observer variation with regard to some physical signs of atopic dermatitis is of a magnitude which argues against their continued use in clinical and epidemiological studies.
TL;DR: It is shown that HRT increases spinal BMD and maintains femoral BMD in postmenopausal RA and is also an effective agent in preserving bone mass in patients taking low-dose corticosteroids.
Abstract: Objective. To assess the effect of hormone replacement therapy (HRT) on bone mass in rheumatoid arthritis (RA) patients treated with and those not treated with steroids.
Methods. Two hundred postmenopausal women with RA (ages 45-65 years) were randomly allocated to receive transdermal estradiol (hormone replacement therapy; HRT) (50 μg daily) or calcium supplementation (400 mg daily) for 2 years. Forty-two of the patients (21%) were taking corticosteroids. Bone mineral density of the lumbar spine (BMDLS) and of the proximal femur (BMDF) was measured at study entry and at 12 months and 24 months.
Results. In the HRT group overall, mean BMDLS had changed by +2.22% (95% confidence interval [95% CI] +0.72, +3.72) and mean BMDF by −0.41 % (95% CI −1.89, +1.07) after 24 months. In the calcium group, mean BMDLS changed by −1.19% (95% CI −2.29, −0.09) and mean BMDF by −0.56% (95% CI −2.60, +1.48). Differences between treatment groups were significant for the spine only (P < 0.001). In the 21 HRT-treated patients taking steroids, BMDLS increased by 3.75% (95% CI +0.72, +6.78) and BMDF by 1.62% (95% CI −1.27, +4.51).
Conclusion. This study shows that HRT increases spinal BMD and maintains femoral BMD in postmenopausal RA. HRT is also an effective agent in preserving bone mass in patients taking low-dose corticosteroids.
TL;DR: The prolonged use of benzodiazepines throughout pregnancy raised the concern that there may be altered transmitter synthesis and function, leading to neurobehavioural problems in the children, but there has been no significant increase in the incidence of neonatal jaundice and kernicterus in term infants.
TL;DR: A set of tests was designed to cover speed and endurance in walking, stair climbing, standing up from a chair, sit‐ups, arm endurance, grip strength, and peak flow and reliability, validity, and acceptability of each test was examined and recommendations made for their relative utility.
Abstract: The physical performance of chronic pain patients is of major concern both for their assessment and for treatment evaluation. However, there are few widely used physical tests, a shortage of reliability and validity data on published tests, and an over-reliance on self-report or on clinical measures of dubious generalisability. A set of tests was designed to cover speed and endurance in walking, stair climbing, standing up from a chair, sit-ups, arm endurance, grip strength, and peak flow. Standard instructions and testing conditions were used by a trained tester on a population of chronic pain patients before and after a cognitive-behavioural chronic pain management programme. Reliability, validity, and acceptability of each test was examined, and recommendations made for their relative utility.
Journal Article•
TL;DR: The findings demonstrate the modelling of B-cell lymphoma bearing the t(14;18) translocation and the ability to modify the lymphoma process with the use of antisense oligonucleotides to the BCL-2 gene confirming that it plays an essential role in the development of malignancy.
Abstract: The t(14;18) translocation is found in the majority follicular lymphomas and some high grade B-cell lymphomas. This is results in deregulation of the BCL-2 gene and appears to play a role in oncogenesis. Various numbers of cells from a cell line derived spontaneously from a patient with B-cell lymphoma bearing the t(14;18) translocation and negative for the Epstein-Barr virus (EBV) were injected by IP, IV, and SC routes into SCID mice. The mice developed lymphoma bearing the t(14;18) translocation with as few as 5 x 10(6) cells within 28 days. This was determined by histological examination. The higher the cell inoculation the more rapidly the lymphoma developed. Engraftment of the tumour cells was determined by PCR for the t(14;18) breakpoint region on peripheral blood samples and could be detected prior to development of overt lymphoma. Having established a lymphoma model the cells were treated with antisense oligonucleotides to the first open reading frame of the BCL-2 gene prior to inoculation of the SCID mice. Control treatments with sense and nonsense oligonucleotides was also performed. At 28 days the sense, nonsense and untreated cell SCID mice had developed lymphoma, however, the antisense treated group failed to develop lymphoma. The findings demonstrate the modelling of B-cell lymphoma bearing the t(14;18) translocation and the ability to modify the lymphoma process with the use of antisense oligonucleotides to the BCL-2 gene. Reduction of the BCL2 protein suppresses the oncogenic potential of these lymphoma cells confirming that it plays an essential role in the development of malignancy.
TL;DR: In this article, the authors studied whether whole-body positron emission tomography (PET) with 18F-fluorodeoxyglucose (18FDG) would improve the preoperative detection of metastases.
TL;DR: Of the molds, Scytalidium species can infect both fingernails and toenails, as well as adjacent skin, and represent 3% of the nail infections in a temperate country such as the United Kingdom but a much higher proportion in tropical countries.
Abstract: Cases of onychomycosis represent up to 30% of diagnosed superficial fungal infections and are caused by three groups of fungi: dermatophytes, yeasts, and nondermatophytic molds. The majority of toenail infections are caused by dermatophytes; Trichophyton rubrum is isolated with the greatest frequency. In infections of fingernails, Candida species can be isolated as frequently as the dermatophytes. Of the molds, Scytalidium species can infect both fingernails and toenails, as well as adjacent skin, and represent 3% of the nail infections in a temperate country such as the United Kingdom but a much higher proportion in tropical countries. Other molds such as Scopulariopsis, Acremonium, and Aspergillus species can infect damaged nails. The isolation of a dermatophyte is always considered indicative of infection, but the presence of other molds, which may be aerial contaminants, must be interpreted with care.
TL;DR: It is concluded that the practical aspects ofEnteral feeding after liver transplantation are surmountable and that enteral feeding is as effective at maintaining nutritional status as total parenteral nutrition, and has potential benefits in terms of reduced complications and costs.
TL;DR: Two of the six PNP sera specifically reacted with the extracellular domain of recombinant pemphigus vulgaris antigen protein, indicating that pem PHV antigen may be involved in PNP, and the immunoblot technique may be a useful tool to unravel the complex mechanisms of the PNP antigens.
TL;DR: It is confirmed that epilepsy as a primary neuropsychiatric event is significantly associated with moderate-to-high titers of IgG aCL in SLE patients and suggested that aPL could have a role in the etiopathogenesis of epilepsy in Sle patients.
Abstract: Objective. To determine whether the occurrence of seizures is correlated with the presence of serum antiphospholipid antibodies (aPL) in systemic lupus erythematosus (SLE) patients.
Methods. The study included 221 unselected patients with SLE. Of these, 21 patients with epileptic seizures not attributed to any cause other than SLE were identified. Epilepsy was diagnosed by clinical history and electroencephalography. Blood samples were tested for the presence of antibodies to cardiolipin (aCL, IgG and IgM isotypes) and lupus anticoagulant (LAC).
Results. LAC was detected in 43.8% of the patients with epilepsy and in 20.8% of controls (P = 0.057). A statistically significant association was found between moderate-to-high titers of IgG aCL and the presence of seizures (P = 0.02). Brain computed tomography and/or magnetic resonance imaging scanning was performed in 14 patients. All patients with abnormal features found on these tests had positive aPL (P = 0.03). Nine patients (42.9%) had at least 1 of the classic features associated with the aPL syndrome.
Conclusion. We confirmed that epilepsy as a primary neuropsychiatric event is significantly associated with moderate-to-high titers of IgG aCL in SLE patients. Our results suggest that aPL could have a role in the etiopathogenesis of epilepsy in SLE.
TL;DR: The results indicate that certain CF patients are more susceptible to oxidative damage, even in the presence of relatively normal concentrations of the major plasma antioxidants; these patients may benefit from increased antioxidant consumption.
Abstract: Patients with cystic fibrosis (CF) may be more susceptible to oxidative cell injury than normal healthy children due to both the impaired absorption of antioxidant nutrients and the increased oxidative stress caused by chronic pulmonary infections. The purpose of this study was to examine whether markers of oxidative damage to lipids (malondialdehyde-like substances and lipid hydroperox-ides) and proteins (protein carbonyls) were present in the plasma of CF patients. Mean values (± SD) of thiobarbi-turic acid-reactive substances were significantly higher in patients (6.93 ± 1.47 μmol/L; n = 25) than in controls (5.84 ± 0.59 μmol/L; n = 10). FFA hydroperoxides were not detected in control subjects (the detection limit of the assay was 0.02 μmol/L), but in 11 of the 33 CF patients studied they were found in a range of 0.03–0.34 μmol/L. Plasma protein carbonyl concentrations did not differ significantly between the two groups (p = 0.076), although a much wider distribution was observed in the CF patients (range 0.17–5.64 nmol/mg protein) than in the control group (range 0.24–1.55 nmol/mg protein). No correlation was found between thiobarbituric acid-reactive substances and FFA hydroperoxides or between either of these markers and protein carbonyl content. Concentrations of plasma vitamin E, vitamin C, and protein sulfhydryls were within the normal ranges in both control subjects and CF patients. The concentration of uric acid was significantly reduced (p < 0.01) in the CF group (204 ± 96.99 μmol/L) compared with that in control subjects (352 ± 81.11 μmol/L), but reduction in plasma levels of this antioxidant did not correlate with increased markers of free radical damage. These results indicate that certain CF patients are more susceptible to oxidative damage, even in the presence of relatively normal concentrations of the major plasma antioxidants; these patients may benefit from increased antioxidant consumption.
TL;DR: Monoclonal aCL may recognize a cryptic epitope, which appears as a result of beta 2-GPI binding to anionic PLs or to polystyrene with carboxyl groups.
Abstract: Objective To elucidate the specificity of anticardiolipin antibodies (aCL) from patients with the antiphospholipid syndrome (APS) to various phospholipids (PLs), DNA, and beta 2-glycoprotein I (beta 2-GPI). Methods Five monoclonal aCL were established from peripheral blood lymphocytes of 3 patients with the APS. The reactivity of monoclonal aCL with various PLs, with DNA, and with beta 2-GPI was examined by enzyme-linked immunosorbent assay (ELISA). Results All of the monoclonal aCL bound to anionic PLs, only in the presence of beta 2-GPI. Neither monoclonal aCL nor beta 2-GPI bound to DNA. Monoclonal aCL bound to solid-phase beta 2-GPI on polystyrene ELISA plates that had carboxyl groups on their surface, but did not react with solid-phase beta 2-GPI on ordinary polystyrene plates. A mixture of beta 2-GPI and CL inhibited the binding of monoclonal aCL to beta 2-GPI, but CL or beta 2-GPI alone did not. Conclusion Monoclonal aCL may recognize a cryptic epitope, which appears as a result of beta 2-GPI binding to anionic PLs or to polystyrene with carboxyl groups.
TL;DR: These patients represent an unusual, poorly recognized form or expression of dystrophic epidermolysis bullosa which has features in common with a variety of acquired inflammatory dermatoses.
Abstract: We report a study of eight unrelated adult patients with a highly distinctive phenotype of dystrophic epidermolysis bullosa. It is characterized clinically by pruritus, lichenified or nodular prurigo-like lesions, violaceous linear scarring, occasional trauma-induced blistering, excoriations, milia, nail dystrophy and, in some cases, albopapuloid lesions on the trunk. The scarring is most evident on the limbs, particularly on the shins, with relative sparing elsewhere. Intact blisters are rarely seen. Physical signs were present at birth in three patients, but in the others skin manifestations were first noticed between 6 months and 10 years of age. Five cases are sporadic, but three of the eight patients have a history of familial involvement, with autosomal dominant inheritance in two cases and recessive transmission in the other case. Studies of the dermal-epidermal junction showed alterations in the number and ultrastructure of anchoring fibrils in lesional, perilesional and non-lesional skin, consistent with a diagnosis of dominant or localized recessive dystrophic epidermolysis bullosa. These patients represent an unusual, poorly recognized form or expression of dystrophic epidermolysis bullosa which has features in common with a variety of acquired inflammatory dermatoses.
TL;DR: The dramatic events that accompany thymic involution during pregnancy are discussed, and the possible immune, neural and endocrine interactions that may occur are traced.
TL;DR: A detailed study of EEGs of patients with an unequivocal diagnosis of juvenile myoclonic epilepsy showed a high prevalence of focal EEG abnormalities, which should not be misconstrued as indicative of partial epilepsy.
Abstract: A detailed study of EEGs of patients with an unequivocal diagnosis of juvenile myoclonic epilepsy (JME) showed a high prevalence of focal EEG abnormalities. Focal slow waves, spikes, and sharp waves and focal onset of the generalized discharge were present in 36.7% of EEGs in our patients with JME. In more than half of the patients, at least one EEG showed focal abnormalities. These features should not be misconstrued as indicative of partial epilepsy.
TL;DR: In this paper, a study of 86 patients with 12 months of follow-up was designed to determine whether topical corticosteroids or plasmin inhibitors have an effect on the outcome of photorefractive keratectomy.
TL;DR: Examining the conjunctival fornix from unselected autopsies with no prior history of Conjunctival or ocular disease for the presence of organized MALT suggests that MALT is not found in the normal human conjunctiva but is acquired during life in a proportion of apparently asymptomatic individuals.
Abstract: The recent description of conjunctival lymphomas with features of lymphomas that arise in mucosa-associated lymphoid tissue (MALT) infers the presence of MALT in the human conjunctiva. Some authors suggest that organized MALT is found in the normal human conjunctiva, but others disagree. In order to resolve this problem, we have examined the conjunctival fornix from unselected autopsies with no prior history of conjunctival or ocular disease for the presence of organized MALT. In only 31 per cent of cases was organized lymphoid tissue found with the morphological and immunophenotypic features of MALT. This finding suggests that MALT is not found in the normal human conjunctiva but is acquired during life in a proportion of apparently asymptomatic individuals.