Comment on analysis of mutations in genes of the follicle-stimulating hormone receptor in ovarian granulosa cell tumors.
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Female↗
Biomedical subjects
S Hussein
Publications and source records attributed to S Hussein.
[Operative management of trigono-atrial lesions].
Trigono-atrial-Lesions are microsurgically serios accessible, the results of transcortical aproaches are difficult and frequently unsatisfactory. The microsurgical anatomy of the trigono-atrial region will be studied on 100 brain hemispheres (the posterior cerebral arteries were injected selective on 70 hemispheres). According to the anatomical findings, an interhemispheric microsurgical approach has been developed. The operative results of 25 patients with different atrial lesions are presented. There was no operative mortality, the postoperative morbidity was 12%, in 24% (n = 6) the preoperative state was still unchanged, in 12 cases (48%) we note a normal neurological and neuropsychological postoperative status. In 4 patients (16%) the neurological symptoms are postoperatively improved. According to these first results, the described transatrial approach seems to be a real alternative for careful selected meanly leftsided lesions of the trigone.
Adult↗
Multilineage mobilization of peripheral blood progenitor cells in humans following administration of PEG-rHuMGDF.
The most important physiological regulator of megakaryocytopoiesis is the ligand for the c-mpl receptor (thrombopoietin/megakaryocyte growth and development factor, MGDF). We examined the effect of pegylated-recombinant human MGDF (PEG-rHuMGDF): patients received PEG-rHuMGDF at doses of 0.03, 0.1, 0.3 or 1.0 microg/kg/d or placebo for 10d maximum in a double-blinded randomized study. There was a dose-dependent elevation in circulating platelet counts but no alteration in erythrocyte or total leucocyte counts. The number of bone marrow megakaryocytes was increased approximately 2-fold. The frequency of bone marrow progenitor cells was not altered. In contrast, both to the bone marrow results and to published pre-clinical data, there was a dose-dependent mobilization into the blood of progenitor cells of multiple cell lineages. Increased levels of Meg-CFC (maximum increase 30-fold), day 7 and day 14 GM-CFC and BFU-E were demonstrated at doses of 0.3 and 1.0 microg/kg/d PEG-rHuMGDF. At 0.1 microg/kg/d, mobilization of Meg-CFC alone occurred in two-thirds of patients. Maximum blood levels of progenitor cells occurred at day 12. Thus, administration of PEG-rHuMGDF to humans resulted in mobilization of progenitor cells of multiple lineages despite its 'lineage-specific' activity on mature cell development.
Adult↗
A novel form of hereditary sideroblastic anaemia with macrocytosis.
We describe a pedigree with maternally inherited sideroblastic anaemia in which the red cells are dimorphic with a raised MCV. To our knowledge, this form of hereditary sideroblastic anaemia (HSA) has not been reported previously. 16 members of the family were investigated, revealing eight affected members. Two further family members were not tested but were presumed affected on the histories available. The proband, born in 1967, presented during pregnancy with a macrocytic anaemia (Hb 7.0 g/dl, MCV 106 fl) and a dimorphic red cell picture. Post partum, a bone marrow biopsy showed hypercellularity, mild dyserythropoiesis and ring sideroblasts. Cytogenetics were normal. Other causes of macrocytosis were excluded. Six other family members (three female, three male) have similar findings. There is no evidence of paternal transmission. An additional female relative who presented in 1992 with refractory anaemia with excess blasts in transformation and a dimorphic blood film, died from progression to AML. Affected members show a raised metal-free red cell protoporphyrin level suggestive of a defect at the level of Fe2+ incorporation into protoporphyrin. We propose that this form of HSA is due to a mitochondrial mutation. A search for deletions or point mutations in the mitochondrial DNA is currently underway.
Adult↗
Clinical predictors of the psychosocial long-term outcome after brain injury.
The correlation of clinical with psychological and social data is an attempt to find predictors of the definite long-term outcome after brain injury. 34 patients were reexamined 3 to 8 years after the accident using a number of psychological tests. Additionally, life quality was defined and evaluated. Only patients with an initial Glasgow Coma Scale-Score of 3-12, an intracranial traumatic lesion on computertomography and age 16-65 years at the time of accident were included in this study. Patients exhibited a uniform pattern of disturbances in psychosocial long-term outcome. These disturbances were compared with initial clinical data: memory, attention and learning were significantly correlated with the duration of coma and the presence of additional extracerebral injuries. From the initial computerized tomography, the findings 'compression of basal cisterns' and 'intracerebral contusion' showed to be predictors of the cerebral function. Late social status and behavior, defined as quality of life, were clearly related with initial clinical findings. In conclusion, there are early clinical predictors of the long term social and psychological outcome after brain injury.
Adolescent↗
Thrombopoietic effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in patients with advanced cancer.
BACKGROUND: Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) is a potent stimulator of megakaryocyte colony formation and platelet production. It is likely to be useful in the management of severe thrombocytopenia. To determine its clinical activity and safety, we gave it to patients with advanced cancer before chemotherapy. METHODS: Patients were randomly assigned to receive either PEG-rHuMGDF or placebo in a three to one ratio. PEG-rHuMGDF was given at a dose of 0.03, 0.1, 0.3, or 1.0 microgram/kg body weight. The study drug or placebo were administered daily by subcutaneous injection for up to 10 days or until a target platelet count was reached. FINDINGS: 17 patients, median age 59 years, received either PEG-rHuMGDF (13 patients) or placebo (four patients). PEG-rHuMGDF produced a dose-dependent increase in platelet counts. Patients given placebo. 0.03, and 0.1 microgram/kg of PEG-rHuMGDF had median increases in platelet counts of 16%, 12%, and 39%. Those receiving 0.3 and 1.0 microgram/kg of PEG-rHuMGDF had an increase in blood platelets of between 51% and 584%. Platelets rose from day 6 of PEG-rHuMGDF administration and continued to rise after stopping the drug. The platelet count peaked between days 12 and 18 and remained above 450 x 10(9)/L for up to 21 days. There were no alterations in white-blood-cell count or haematocrit, and low toxicity. Platelets taken from patients during PEG-rHuMGDF administration and at the time of peak platelet count were morphologically and functionally normal. INTERPRETATION: The potency with which PEG-rHuMGDF stimulates platelet production and its low toxicity indicate that this is likely to be a useful agent for the management of thrombocytopenia.
Dose-Response Relationship, Drug↗
In vivo administration of anti-murine CD3 monoclonal antibody induces selective, long-term anergy in CD8+ T cells.
The purpose of this study was to determine the short-term and long-term effects of repeated daily administration of low dose anti-CD3 monoclonal antibody (mAb) on CD4+ and CD8+ T cell number and function. Daily (7 days) administration of low doses (5 microg) of mitogenic (whole) or nonmitogenic (F(ab')2, fragments) anti-CD3 mAb resulted in depletion of CD4+ and CD8+ T cells in both lymph node and spleen that, in the case of whole mAb, persisted for several months in thymectomized animals. CD3+ cells obtained from thymectomized animals treated with whole but not F(ab')2 fragments of anti-CD3 mAb demonstrated decreased proliferation to anti-CD3 mAb in vitro (on a per cell basis as compared with control animals). Although purified CD4+ cells from animals treated with whole mAb demonstrated only slightly decreased proliferative responses to anti-CD3 mAb in vitro, purified CD8+ cells demonstrated an almost complete loss of their proliferative response. Studies in thymectomized animals demonstrated that the profound CD8+ cell hyporesponsiveness persisted for at least 5 months after anti-CD3 treatment. These effects were not observed in nonthymectomized animals, however, suggesting that recovery of CD8+ T cell function is caused by repopulation of lymphoid organs by thymic-derived CD8+ T cells. Additional studies with purified CD8+ cells from anti-CD3 mAb-treated animals indicated that the hyporesponsiveness was not caused by alterations in T cell receptor (TCR) expression. However, proliferative responses of anergic CD8+ T cells to phorbol ester and ionomycin were comparable to those of control CD8+ T cells. After in vitro stimulation, CD8+ cells from anti-CD3 treated animals did not produce interleukin (IL)-2, and although they retained their ability to upregulate IL-2 receptor expression (albeit reduced by about 50% compared with CD8+ cells from control animals), proliferative responses were not restored by addition of exogenous IL-2. In addition to IL-2 receptor expression, CD8+ cells from anti-CD3-treated animals also demonstrated an ability to upregulate CD44 and LFA-1 expression upon reexposure to anti-CD3 mAb in vitro. In conclusion, treatment with daily administration of low doses of whole or F(ab')2 fragments of anti-murine CD3 mAb induces significant T cell depletion in secondary lymphoid organs and does not seem to alter CD4+ proliferative responses in vitro, but whole mAb (and not F(ab')2 fragments) profoundly suppresses CD8+ proliferative responses. The profound hyporesponsiveness of CD8+ T cells induced by whole anti-murine CD3 mAb (1)persists for at least persists for at least several months, (2) is characterized by decreased IL-2 production and responsiveness to IL-2, and (3) recovery of CD8+ cell function is likely mediated by repopulation of lymphoid organs by thymic-derived CD8+ cells.
Animals↗
An immunohistochemical study of TAL-1 protein expression in leukaemias and lymphomas with a novel monoclonal antibody, 2TL 242.
Fifty formalin fixed, paraffin-embedded cases of T-acute lymphoblastic leukaemia (T-ALL) from 12 bone marrow trephines and 38 lymph nodes were stained with a new monoclonal antibody, 2TL 242, raised against recombinant TAL1 protein. The antibody recognizes TAL-1 polypeptides of molecular weight 39 and 41 kD (full length). In addition, a variety of other leukaemias and lymphomas were also stained with 2TL 242. Twenty-four of the 50 cases of T-ALL showed nuclear positivity, ranging from 10 to 90 per cent of leukaemic cells. A positive staining reaction was nuclear and stippled in pattern. Nuclear staining was not seen in any other type of leukaemia or lymphoma. Five cases of follicular lymphoma showed diffuse cytoplasmic staining of variable intensity. Although some background staining is obtained with this antibody, positive nuclear staining is easily distinguishable. This monoclonal antibody has a potential role in primary diagnosis and in the detection of minimal residual disease in T-ALL.
Antibodies, Monoclonal↗
Superselective intra-arterial amytal (Wada test) in temporal lobe epilepsy: basics for neuroradiological investigations.
We describe the angioarchitecture of the medial temporal region as a basis for modified superselective Wada tests in patients with temporal lobe epilepsy. Possible functional deficits following the injection of amytal, depending on the superselective placement of the microcatheter in the medial temporal arteries, are discussed. The individual blood supply in each patient determines the ideal super-selective positioning of the micro-catheter.
Amobarbital↗
Lung compensation in total body irradiation: a radiographic method.
Using megavoltage radiography and a composite chest phantom, exit dose measurements were carried out to establish an empirical relationship between the optical film density and the corresponding equivalent thickness of overlying phantom material. Results for Co-60, 4-MV, and 10-MV photons show that the relationship depends on the sensitometric properties of the radiographic film and the photon beam quality. For an actual patient undergoing total body irradiation (TBI), a chest radiograph in treatment geometry provides the optical density information that is used to calculate the tissue deficit in the lung region. The compensators are made of lead whose thickness is chosen to replace the tissue deficit over the lung region. The validity of the method is established both by comparing its results to that obtained from multiple-slice computed tomography (CT) data for 4- and 10-MV photons, and by in-phantom thermoluminescent dosimetry (TLD) for Co-60, 4-MV and 10-MV beams.
Biophysical Phenomena↗
Variation of electron beam uniformity with beam angulation and scatterer position for total skin irradiation with the Stanford technique.
PURPOSE: The influence of different scatterer-degraders and beam angulations on beam uniformity for total skin electron irradiation using the six dual beam Stanford technique is investigated. METHODS AND MATERIALS: The 6 MeV high dose rate total skin electron irradiation mode on a linear accelerator was used. Beam profiles and percentage depth doses in the patient plane for single, dual, and six dual beams were measured for different dual beam angulations and acrylic scatterer-degraders of different thicknesses mounted on the treatment head or in front of the patient in the treatment plane. RESULTS: It is demonstrated that, with the same electron nominal energy, total skin irradiation techniques with different beam penetrations can be obtained by inserting various beam scatterer-degraders into the beam, either mounted on the accelerator head or close to the patient. For our patient treatment, a beam penetration was selected so that the 80% dose lay at 8-9 mm and the 50% dose at 15-16 mm depth. This was achieved by mounting a 0.32-cm thick acrylic beam scatterer-degrader on the accelerator head. A uniform vertical profile was obtained for gantry angulations of +/- 21 degrees. CONCLUSIONS: To implement a total skin electron irradiation technique using the Stanford method, the required depth of penetration needs to be selected. Based on this, the appropriate combination of scatterer-degraders and dual beam angulations to produce a uniform beam in the treatment plane needs to be determined. Different techniques with different beam penetrations can be developed using the same high dose rate mode on the linear accelerator by a proper choice of scatterer-degraders and beam angulations.
Humans↗
Total body irradiation with a sweeping 60Cobalt beam.
PURPOSE: This article describes the physical, technical, and dosimetric aspects of total body irradiation (TBI). METHODS AND MATERIALS: The continuous head swivel motion of a standard 60Cobalt unit has been used to obtain a sweeping beam that encompasses the entire length of the patient in TBI. A perspex beam flattener designed to remove the inverse square fall-off in beam intensity along the sweep axis provides a 90% field length of 200 cm in air at a treatment source-to-skin distance of 160 cm. The anterior-posterior parallel pair setup permits accurate placement of customized lead compensators to limit the dose to lungs. RESULTS: Measured beam profiles, dose buildup curves, and percentage depth dose for the technique are presented. With compensators in place, the variation in lung dose is shown to be within +/- 5% of the prescribed tumor dose. CONCLUSIONS: A sweeping beam TBI technique has been devised using a standard 60Cobalt unit. The technique allows the patient to be treated in supine and prone positions, which facilitates the accurate placement of lung compensators to limit the dose to lung tissue.
Cobalt Radioisotopes↗
SCL/Tal-1 expression in T-acute lymphoblastic leukemia: an immunohistochemical and genotypic study.
A comparative study of the immunohistochemical (Stem cell leukemia/T-cell acute leukemia [SCL/TAL-1] protein expression) and genotypic (deletions in the SCL/tal-1 gene) findings in T-acute lymphoblastic leukemia (T-ALL) is presented. Formalin-fixed tissue from 50 cases of T-ALL were stained with a novel monoclonal antibody, 2TL 242, which recognizes SCL/TAL-1 protein. Twenty-four cases showed nuclear immunolabeling of leukemic cells. Nuclear positivity was not evident in any other type of leukemia or lymphoma tested with the antibody. Genotypic analysis of 25 cases of T-ALL showed a deletion involving the SCL/tal-1 gene in nine cases. These results suggest that protein expression is not dependent on derangement of the SCL/tal-1 gene, because immunohistochemical detection of the protein was noted in the presence and absence of a tal-d1 deletion.
Base Sequence↗
Examination of the effects of emotional disturbance and its detection on general practice patients' satisfaction with the consultation.
BACKGROUND: A patient's satisfaction with a consultation may be influenced by many factors relating to both patient and doctor. AIM: This study set out to examine the effects of emotional disturbance and its detection on general practice patients' satisfaction with the consultation. METHOD: A prospective study involving 893 adult patients attending 12 general practitioners in Glasgow was carried out. Questionnaires were completed by general practitioners after consecutive surgery consultations. Patients completed forms assessing mental state and satisfaction with inter-personal aspects of the consultation. RESULTS: Patients reporting frank psychological disturbance tended to express more dissatisfaction with the inter-personal aspects of the consultation. This effect was alleviated in the majority by recognition of the disturbance by the general practitioner. General practitioners differed markedly in their assessment of the psychological component of consultations. Fewer dissatisfied patients were found in the surgeries of doctors who tended to rate the psychological component of consultations more highly. In contrast, the general practitioner's overall accuracy of diagnosis of psychological distress was a poor predictor of the proportion of dissatisfied patients. CONCLUSION: This preliminary study suggests that a tendency among doctors to assign importance to the psychological component of consultations may enhance elements of patient satisfaction. It is not clear whether this [psychological-mindedness' is an attribute which can be learnt. To resolve this uncertainty, studies are needed of the effects on patients of educational interventions designed to increase general practitioners' sensitivity to psychological distress.
Adult↗
Bradycardia associated with fluoxetine in an elderly patient with sick sinus syndrome.
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Aged↗
Community-acquired infections.
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Anti-Bacterial Agents↗
Analysis of polymorphic variation in drug metabolism: III. Glucuronidation and sulfation of diflunisal in man.
The urinary excretion of diflunisal (D) and its metabolites diflunisal sulfate (DS), diflunisal phenolic glucuronide (DPG), and diflunisal acyl glucuronide (DAG) were measured in 110 healthy, drug-free Caucasian volunteers given 50 mg of diflunisal by mouth. When expressed as fractional recoveries, DS, DPG, and DAG were strongly negatively correlated with one another. Metabolic ratios, on the other hand, correlated positively and tended to localize variability within a single enzyme pathway. Thus, females using estrogen-containing oral contraceptives were shown to excrete 50% less DS and 20% more DAG than non-users, and recoveries of DS were reduced by about 30% in cigarette smokers. Kernel density analyses of the log metabolic ratios of DS and DPG were broad-based and unimodal. However, kernel density estimates of the distribution of log metabolic ratios of DAG showed 3 peaks, 1 of which (an extensive metabolizer polymorph) could be removed by excluding contraceptive-using females. Similarly, there were 2 poor metabolizer peaks in the distribution of log metabolic ratios of DS attributable to cigarette smoking and, in females, use of an oral contraceptive. Thus, we conclude that the metabolism of diflunisal is altered by cigarette smoking and oral contraceptives, and that kernel density estimation, as applied to log metabolic ratios, is a sensitive and specific method for detection of polymorphic variation in drug metabolism.
Adolescent↗
[Bicycle rider's ulnar nerve paralysis].
The ulnar neuropathy in bicycle riders is a less common occurrence, due to a local damage of the nerve on the level of the ulnar tunnel. It has been described in neurological literature only a few times, and hence its good prognosis is not sufficiently known. Within a short time two patients of this disease were transferred to our clinic for operation. After a local space-occupying growth in the tunnel could be excluded by MR or sonography of the wrist, we discouraged performance of an operative procedure. The patients' complaints and the neurological deficits vanished in a few weeks. Ulnar neuropathy in bicycle riders is therefore a syndrome for which even in the case of severe deficit an operation is not recommended.
Bicycling↗