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Biomedical subjects

G Becker

Publications and source records attributed to G Becker.

At least 91 records · Page 5Linked to original sources
PubMed1998

p16/MTS1 inactivation in ovarian carcinomas: high frequency of reduced protein expression associated with hyper-methylation or mutation in endometrioid and mucinous tumors.

Inactivation of the tumor-suppressor gene p16 (MTS1/ CDKN2/INK4a) has been described in various human malignancies. Although p16 deletion has been found in various ovarian tumor cell lines, p16 inactivation by homozygous deletion or mutation has been reported only sporadically in primary ovarian carcinomas. In a comprehensive study, we analyzed p16 protein expression by immuno-histochemistry (IHC) on paraffin sections of 94 primary ovarian carcinomas of different histological subtype. Loss of expression was detected in 19 primary tumors (20%), mainly mucinous and endometrioid carcinomas. To reveal the cause of suppressed expression, we performed (i) analysis of homozygous deletions by comparative PCR after micro-dissection, (ii) mutation analysis by single-strand conformation polymorphism analysis and subsequent direct sequencing and (iii) methylation-specific PCR to determine the methylation status of 5'-CpG islands. Loss of or weak p16 expression was caused by hyper-methylation (12/19 IHC-negative cases), somatic mutation (10 tumors) or homozygous deletion (1 case). Aberrant p 16 results by one of these methods were detected in 71-79% of endometrioid and mucinous, but in only 10% of serous-papillary, carcinomas. Our data suggest that p16 inactivation is a typical feature of certain subtypes of ovarian carcinoma.

Adenocarcinoma, Mucinous↗
PubMed1998

Imaging the pre- and postsynaptic side of striatal dopaminergic synapses in idiopathic cervical dystonia: a SPECT study using [123I] epidepride and [123I] beta-CIT.

There is increasing evidence that a dysfunction of the dopaminergic system may be involved in the pathogenesis of idiopathic dystonia. To visualize possible alterations of the pre- and postsynaptic side of striatal dopaminergic synapses, SPECT studies using the radiotracers [123I] epidepride and [123I] beta-CIT were performed in 10 patients with idiopathic cervical dystonia. Eleven age- and sex-matched subjects served as controls. [123I] Epidepride is a new highly affine marker of D2 receptors, and [123I] beta-CIT binds to dopamine transporters on dopaminergic nerve endings. [123I] Epidepride binding was significantly reduced in both striata of dystonia patients compared with controls (p < 0.05). In contrast, striatal [123I beta-CIT uptake did not differ from controls. We conclude that dopaminergic dysfunction in idiopathic focal dystonia mainly involves postsynaptic mechanisms and suggest a disturbance of the indirect pathway of the motor circuit resulting in a disinhibited thalamocortical stimulation.

Adult↗
PubMed1998

The disclosure decision: concerns and issues of parents of children conceived through donor insemination.

OBJECTIVE: The purpose of our study was to examine the disclosure decision by parents of children conceived by donor insemination. STUDY DESIGN: A qualitative component of a self-administered questionnaire mailed to 184 couples who had become parents by donor insemination encouraged respondents to volunteer their written comments, concerns, or opinions about their disclosure decision. RESULTS: A total of 70 men and 86 women submitted written comments indicating that 54% did not plan to disclose the donor insemination treatment (nondisclosers), 30% indicated they would (disclosers), and 16% remained undecided. The only significant relationship between the disclosure decision and expressed concern was with regard to confidentiality and honesty (chi2 = 99.9, p < 0.05). CONCLUSIONS: Whether parents viewed the disclosure issue as one of honesty (disclosers) or confidentiality (nondisclosers) was the major determinant in the decision of whether to tell children about their donor insemination origin. There was no association between disclosure status or gender and expressed concerns about parenting, children, or family relations.

Adult↗
PubMed1998

Pattern of graft- and host-specific MHC class II expression in long-term murine cardiac allografts: origin of inflammatory and vascular wall cells.

In solid-tissue allografts, donor vascular cells as well as recipient inflammatory cells can express MHC class II molecules. However, it is uncertain how much residual donor endothelium persists and to what extent donor versus recipient MHC class II expression can contribute to the ongoing immune response, especially in long-term grafts. To establish the origin of class-II-expressing cells in the allograft, we evaluated the expression of donor- or recipient-specific MHC class II molecules in murine cardiac allografts. Donor hearts from BALB/c (H-2d) mice were transplanted into C57BL/6 (B6, H-2b) recipients; B6 isografts served as controls. Untreated allografts ceased functioning at approximately 7 days with severe parenchymal rejection. Allografts from recipients treated with anti-CD4 and anti-CD8 MAbs after transplantation were explanted at 8 to 12 weeks and demonstrated intimal fibroproliferative lesions with a mild parenchymal mononuclear cell infiltrate. Class II expression in isografts was limited to epicardial macrophages. Both acutely rejecting and long-term allografts contained abundant macrophages expressing recipient class II molecules. Occasional cells (passenger leukocytes) in untreated, acutely rejecting allografts bore donor class II molecules; long-term allografts contained few such cells. In contrast, vascular endothelial and medial smooth muscle cells consistently expressed donor class II molecules. These results suggest that ongoing MHC class II expression in donor vascular cells, as well as in recipient macrophages, may contribute to sustained activation of host T cells with consequent release of cytokines that ultimately promote the development of graft arteriosclerosis.

Actins↗
PubMed1998

Interferon-gamma-secreting T-cell populations in rejecting murine cardiac allografts: assessment by flow cytometry.

Interplay between T-helper-1 (Th1) and T-helper-2 (Th2) cells is considered important in the development of acute allograft rejection and many other immune-mediated disease processes. Existing methods for evaluating expression of Th1 and Th2 cytokines, including reverse transcriptase polymerase chain reaction (RT-PCR), RNase protection assay (RPA), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) all have limitations; alternate techniques to quantify cell populations expressing specific cytokine proteins, generate statistically analyzable data, and allow simultaneous identification of cytokine-secreting cell type are needed. To this end, we adapted a flow cytometric technique for intracellular cytokine immunofluorescence staining for use with cells isolated from solid tissue. To demonstrate the utility of the method, we determined the number of CD4+ and CD8+ cells secreting the prototypical Th1 and Th2 cytokines, interferon (IFN)-gamma, and interleukin (IL)-4 in acutely rejecting murine cardiac allografts. We also measured the cytokine production via ELISA, RPA, and semiquantitative competitive RT-PCR. The number of CD4+ cells producing IFN-gamma increased as rejection proceeded, in agreement with previous data; we detected no IL-4 production at any time, although relatively low numbers of IL-10-producing cells were identified. In addition, a high percentage of CD8+ cells, which outnumber CD4+ cells at day 6 after transplant, also produce IFN-gamma, suggesting that cytotoxic lymphocytes contribute significantly to the local cytokine milieu. This new application of intracellular cytokine staining provides a powerful methodology for studying transplantation immunology. The method may also be easily adapted to the study of other immune-mediated processes.

Animals↗
PubMed1998

Do urinary tract infections trigger chronic kidney transplant rejection in man?

PURPOSE: Urinary tract infections are frequent after kidney transplantation but little is known about the impact on long-term survival. As chronic rejection is the major cause of graft loss in the long term, we retrospectively analyzed the role of urinary tract infections in this process. MATERIALS AND METHODS: We included in the study all adult patients who received kidney transplants at our unit between 1972 and 1991, which ensured followup of at least 5 years, and we focused on the relationship between urinary tract infections and the incidence of chronic rejection episodes. To analyze the influence of urinary tract infections on chronic rejection patients were separated into those in whom biopsy proved chronic rejection developed within the first 5 years after transplantation (chronic rejection group 225) and those without apparent signs of chronic rejection during that period (control group 351). The correlation between urinary tract infections per year and the incidence of chronic rejection was analyzed. RESULTS: Patients with chronic rejection had more urinary tract infections per year than controls. In the first year after transplantation both groups had the highest incidence of urinary tract infections but thereafter the rate of urinary tract infections per year declined. However, the incidence consistently remained higher in the chronic rejection group. This difference reached significance by year 3 after transplantation. Furthermore, a high rate of urinary tract infections correlated with an early onset of chronic rejection. CONCLUSIONS: Urinary tract infections are an important risk factor for the onset of chronic rejection, and early and intense treatment is critical.

Adult↗
PubMed1998

Differentiation between intracerebral hemorrhage and ischemic stroke by transcranial color-coded duplex-sonography.

BACKGROUND AND PURPOSE: The differential diagnosis of intracerebral hemorrhage versus ischemic stroke has critical implications for stroke management. Transcranial color-coded duplex sonography (TCCS) has been shown to identify intracerebral hemorrhages and intracerebral vessel occlusions. We conducted this study to evaluate the sensitivity and specificity of TCCS in this differential diagnosis and in the detection of stroke complications. METHODS: One hundred fifty-one patients (58 women, 93 men; mean age, 65.6 years [range, 32 to 89 years] ) with acute hemiparesis were enrolled in this prospective study. On admission all patients had a complete neurological examination. A cranial CT scan and a sonographic examination of the brain parenchyma and all extracranial and intracranial cerebral arteries were conducted. The sonographer was blinded for the radiological findings. RESULTS: According to CT criteria, 60 patients had an intracerebral hemorrhage and 67 patients had an ischemic stroke, and in 24 patients CT findings were inconclusive, showing neither bleeding nor an ischemic stroke. On sonographic examination, 18 patients (12%) had no sufficient acoustic bone window. Of the remaining 133 patients, 126 (95%) were diagnosed correctly by sonography in agreement with CT. Sonography missed 3 atypical bleedings (2 with upper parietal location). In 4 patients without bleeding, an intracerebral hemorrhage was suspected by TCCS because of increased white matter echo density due to microangiopathy. Stroke complications depicted by CT (disturbance of cerebrospinal fluid circulation, hemorrhagic transformation, midline shift, ventricular bleeding) (n=54) were correctly shown by TCCS in 45 patients (83%). No complication was missed that would have required further treatment. CONCLUSIONS: In comparison to the "gold standard" of CT, TCCS identified stroke complications and differentiated between intracerebral hemorrhage and ischemic stroke with reasonable sensitivity. Thus, if CT is not readily available, TCCS may complement clinical examination in patients with acute stroke. In addition, it may also be useful in detecting stroke complications in the follow-up of stroke patients.

Adult↗
PubMed1998

Reasons for delay in seeking treatment for acute asthma: the patient's perspective.

Increased morbidity and mortality due to asthma suggested the need to investigate whether persons with asthma report delay in seeking medical care during acute asthma exacerbations and the reasons they gave for delay. We interviewed 95 asthmatic adults, 36 men and 59 women, using a critical incident technique to discover how patients responded to acute asthma symptom episodes. Subjects were interviewed once per month for a total of three interviews. All subjects had physician-diagnosed asthma for a mean of 16.8+/-14.5 years. Eighty-six percent of the sample (n=82) reported delay in seeking medical care for severe asthma symptoms. Seven reasons for delay were identified: uncertainty, disruption, minimization, fear of systemic corticosteroid, previous bad experiences in emergency departments, the need to "tough it out" alone, and economic reasons. Seventy-one subjects (86.5%) reported three or more reasons for delay. Thirteen subjects (16%) identified pivotal episodes in which they realized they could die from asthma and as a result, no longer delayed. People with asthma often delay seeking urgent care for acute episodes for a variety of reasons. Some of these reasons are modifiable. Clear directions from health professionals to guide patients in responding to acute asthma episodes are needed. Asthma action plans written by the primary physician may be a positive agent of change for those who delay.

Adrenal Cortex Hormones↗
PubMed1998

Tacrolimus rescue therapy in patients with rejection and long-term dialysis after kidney transplantation.

Therapy with tacrolimus has been proven effective in patients with steroid-resistant rejection episodes. It was the objective of the present study to evaluate the efficacy of tacrolimus in patients with long-lasting primary or secondary non-function (defined as being on dialysis for at least 28 days) converted for biopsy proven acute rejection and to determine parameters of prognostic value. Eight patients with biopsy proven acute interstitial rejection unsuccessfully treated with steroids were converted from a cyclosporine based immunosuppressive regimen to tacrolimus. Three patients were additionally pretreated with OKT3 without success. The tacrolimus whole blood through level was 7.5 +/- 2.6 ng/ml at one week and 8.1 +/- 3.4 ng/ml at one month after conversion. The follow-up period after conversion to tacrolimus ranged from 12-18 months. In four patients hemodialysis was stopped after 78 +/- 49 days (range 36-145 days). One year thereafter, creatinine was 3.9 +/- 2.7 mg/dl. In conclusion, our observations, although obtained in a small number of patients, offer some hope in this selected group and may encourage further studies in patients with long-term dialysis after renal transplantation.

Adult↗
PubMed1998

Knowledge and care of chronic illness in three ethnic minority groups.

BACKGROUND AND OBJECTIVES: Despite advances in medical approaches to the management of chronic illnesses, relatively little is known about how older members of ethnic minority groups view their chronic illnesses or how they manage them in daily life. METHODS: We recruited 35 African-Americans, 61 Latinos, and 55 Filipino-Americans, all over age 50. Criteria for entry into the study was the presence of one or more chronic illnesses. Findings are based on structured and semi-structured questions in one in-depth interview. Qualitative data on transcribed interviews with 151 respondents was analyzed. RESULTS: Comparison of the three groups revealed social and cultural differences and similarities that affected the management of chronic illness. The extent to which respondents demonstrated an understanding of their illnesses as chronic varied considerably, with discernible differences among groups about knowledge of illness and self-care practices. CONCLUSIONS: Our findings showed that although major chronic illnesses were, for the most part, the same for all three groups, each group differed in its response to and management of its illnesses. These findings have implications for the education of physicians in training.

Black or African American↗
PubMed1998

Coronary arteriosclerosis after T-cell-mediated injury in transplanted mouse hearts: role of interferon-gamma.

This study evaluated the contribution of acute parenchymal rejection and interferon (IFN)-gamma to the development of graft arterial disease (GAD) in totally allogeneic murine cardiac transplants. BALB/c (H-2d) hearts were transplanted into wild-type C57BL/6 (B6, H-2b) or B6 IFN-gamma-deficient (GKO) recipient mice. Assessing the role of acute parenchymal rejection in the GAD process involved two different immunosuppression protocols using anti-CD4 and -CD8 monoclonal antibodies (MAbs): virtually complete long-term immunosuppression (denoted as complete immunosuppression) was achieved by administering both MAbs 6, 3, and 1 day before transplantation and weekly thereafter; in contradistinction, a single, early, transient episode of rejection (transient rejection) was attained by administering MAbs beginning 4 days after transplant and then at weekly intervals. The extent and duration of T cell depletion under these two regimens were evaluated using flow cytometric analysis of peripheral blood lymphocytes. After a single injection of MAbs, peripheral blood CD4+ and CD8+ T cell depletion was approximately 98% at 1 week and approximately 88% at 2 weeks. After three injections (analogous to days 6, 3, and 1 before transplant), peripheral blood CD4+ and CD8+ T cell depletion was >98% at 2 weeks and approximately 87% at 4 weeks. Functioning cardiac allografts were removed at 8 and 12 weeks after transplant and analyzed by hematoxylin and eosin, elastic tissue, and immunohistochemical stains, and the severity of parenchymal rejection versus GAD was scored. With complete immunosuppression (antibody before and after transplant), BALB/c allografts showed little parenchymal rejection or GAD, suggesting that persistent depletion of T cells blocked subsequent development of GAD. However, even a single transient acute rejection episode allowed the subsequent development of GAD accompanied by augmented major histocompatibility complex (MHC) class II, VCAM-1, and ICAM-1 expression at 12 weeks; these allografts showed no residual CD4+ or CD8+ T cells. In comparison, allografts undergoing transient rejection in GKO recipients did not develop GAD, despite persistent macrophage and natural killer cell (NK) infiltrates comparable to those seen in wild-type recipients. Moreover, the arterioles of hearts transplanted into GKO recipients showed no or minimal increases in MHC class II, ICAM-1, and VCAM-1 relative to baseline expression. In conclusion, a single episode of allogeneic injury mediated by T cells suffices to evoke subsequent graft arteriosclerosis, even in the absence of additional T-cell-mediated injury, and the process appears to depend on IFN-gamma.

Animals↗
PubMed1998

Frontal brain asymmetry and affective style: a conceptual replication.

Recent studies have demonstrated that positive and negative affective reactivity can be predicted by resting electroencephalographic (EEG) asymmetry in frontal brain regions. These studies used different methods to assess asymmetry and affectivity. The goal of the present study was a conceptual replication of these results and to investigate their independence of employed procedures. Resting EEG of 37 subjects was recorded and affective slides were presented to obtain ratings of subjects' emotional reactions. Different procedures were applied to the data to assess the relation between asymmetries and affective reactivity. Depending on the particular analysis procedure, there were associations between anterior asymmetry and affectivity in line with the published findings, opponent to those findings, or no relation between anterior asymmetry and affective reactivity.

Adult↗
PubMed1998

On the quality of treatment planning systems in radiation therapy.

PURPOSE: To assist in the design of quality assurance activities of 3D treatment planning systems (TPSs), a postal survey has been carried out, addressing TPS users on quality characteristics and their relative importance in clinical routine planning. MATERIAL AND METHODS: The approach as described in ISO/IEC 9126 has been used to analyze TPS quality. Both TPS quality characteristics and how these may be used to establish a quality model are included. A questionnaire on ranking of these TPS quality characteristics has been sent out to the German DEGRO members in February 1997. RESULTS: By the end of July 1997, 90 individual assessments (of 45 physicists, 35 physicians, and 10 radiographers) had been collected. On an importance scale from 1 (very important) to 6 (unimportant), weight factors of 1.71 (portability), 2.84 (maintainability), 3.18 (efficiency), 3.85 (usability), 4.52 (functionality) and 4.90 (reliability) have been determined from the data. From user satisfaction data also obtained from the questionnaire responses, baseline quality indices could be established from the quality model for the RTPs Cadplan, TMS Helax, and Voxelplan. CONCLUSION: The responses highlight the need for TPS quality assurance at the same time along the lines of safety-related, research-oriented, and interactive end-user software systems in radiotherapy treatment planning. Quality assurance activities must take this into account. Their effect can be monitored by using quality indices as derivable from the established quality model.

Germany↗
PubMed1997

Ophthalmoplegia plus: clinical relevance of magnetic resonance tomogaphy findings.

The diagnostic value of magnetic resonance imaging (MRI) in patients with ophthalmoplegia plus was evaluated. Twenty patients in whom the diagnosis of opthalmoplegia plus was clinically and histochemically established underwent magnetic resonance and electrophysiological studies. Three types of neuroradiological abnormalities were found in 14 patients: (1) cerebral and/or cerebellar atrophy (n = 11), (2) hyperintense lesions of the white matter or pyramidal tract (n = 2), or (3) both (n = 1). The diagnostic yield of MRI was low, since clinically or electrophysiologically manifest lesions were missed in 4 cases and the pathological findings were non-specific, since they are seen in several demyelinating diseases. Our results suggest that MRI provides no additional information in patients with manifest ophthalmoplegia plus. We conclude that clinical presentation and evidence of ragged red fibers are the cornerstones in diagnosis of ophthalmoplegia plus.

Adult↗
PubMed1997

Iatrogenic spinal epidural abscesses: early diagnosis essential for good outcome.

Spinal epidural abscess usually arises by hematogenous, lymphatic or venous spread. The frequent use of invasive procedures at the spinal cord such as epidural injections to produce analgesia has led to an increased incidence of iatrogenic abscesses. We describe 8 patients who developed iatrogenic spinal epidural abscesses after paravertebral or intragluteal punctures respectively intravenous catheters to produce analgesia. Deep paravertebral or intragluteal injections were the cause of abscess formation in five, a contaminated intravenous line in two and a peridural catheter in one case. Pain of the affected vertebral column and malaise were the leading symptoms and Staphylococcus aureus was isolated in all cases. Diagnosis was made by means of magnetic resonance (n = 7) or Computed tomography (n = 1). Outcome was excellent with early therapy consisting of laminectomy and/or antibiotic treatment in the six patients treated within two days of appearance of symptoms. Invasive procedures at the spinal cord can lead to iatrogenic spinal epidural abscesses. Physicians dealing with deep punctures and catheter procedures should be aware of early symptoms and signs of an epidural abscess, since early diagnosis and specific therapy are the most important factors for a good outcome.

Abscess↗
PubMed1997

Comparison of transcranial sonography, magnetic resonance imaging, and single photon emission computed tomography findings in idiopathic spasmodic torticollis.

Various lines of evidence suggest that the basal ganglia and thalamus are involved in the pathogenesis of idiopathic dystonia, but unfortunately neuroradiological and pathological data are sparse and controversial. In this study, we have examined 10 patients with spasmodic torticollis by neuroimaging techniques, including transcranial sonography (TS; n = 10), conventional (n = 10) and diffusion-weighted (n = 5) magnetic resonance imaging (MRI), and single photon emission computed tomography (SPECT; n = 10), employing [123I]iodobenzamide (IBZM) as a ligand with a high affinity to the D2 receptor. In seven patients, TS showed small hyperechogenic lesions in the medial segments of the lentiform nucleus contralateral to the side of head deviation. In accordance with the site of TS abnormalities, diffusion-weighted MRI displayed a hyperintense lesion in only one patient, while standard MRI of this area was normal in all patients. SPECT revealed a slight but statistically nonsignificant reduction of IBZM tracer uptake in an area corresponding to the dorsal portions of the striatum in 9 of the 10 patients. TS findings support the hypothesis that structural alternations of the pallidothalamic circuit contralateral to the side of head deviation are involved in the pathogenesis of idiopathic spasmodic torticollis. TS may be more sensitive in detecting basal ganglia alterations than MRI.

Adult↗
PubMed1997

[123I]beta-CIT single-photon emission tomography in DOPA-responsive dystonia.

The radiotracer [123I]beta-CIT is a sensitive marker of dopamine uptake sites that can be used to visualize dopaminergic nerve endings in vivo in the human brain. We report on [123I]beta-CIT single-photon emission computed tomography (SPECT) findings in a patient with DOPA-responsive dystonia (DRD). [123I]beta-CIT SPECT showed a striatal radiotracer uptake in the upper range of normal, indicating intact dopamine transporters and structural integrity of nigrostriatal neurons. This differentiates DRD from clinically similar cases with juvenile-onset parkinsonism with dystonia that have a considerable poorer prognosis. [123I]-beta-CIT SPECT may provide a method equally as useful as fluorodopa positron emission tomography in DRD.

Adult↗