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Biomedical subjects

J Wilkes

Publications and source records attributed to J Wilkes.

At least 19 recordsLinked to original sources

[How did youths deal with their forced sterilisation during the Third Reich? Report of a physician involved].

In 1933, one of the first laws passed by the Nazis in Germany was that to prevent the birth of children with hereditary diseases, which legalised forced sterilisation in Germany and also applied to minors. On Social Welfare Education Day in 1934, the leading physician at the "Anstalt Bethel" (Bethel Institution), Werner Villinger, gave a speech on the experience of sterilisation. A main part of his speech was the description of the reaction, fears, and resistance of the boys involved, and the accuracy of his observations stands in sharp contrast to the ruthlessness of the performance of the sterilisation, which was rooted in unshakeable faith in the necessity of this measure.

Adolescent↗

Distal margin requirements after preoperative chemoradiotherapy for distal rectal carcinomas: are < or = 1 cm distal margins sufficient?

BACKGROUND: Sphincter-sparing alternatives to abdominoperineal resection (APR) in the treatment of rectal cancer often are underused out of concern for inadequate distal margins and local failure. The present study addresses whether sphincter-sparing techniques with distal margins < or = 1 cm adversely influence oncological outcome in patients given preoperative chemoradiotherapy. METHODS: Thirty-seven patients with rectal cancer < or = 8 cm from the anal verge were enrolled in the study. Preoperative external beam radiotherapy (5400 Gy) was administered together with continuous infusion of 5-fluorouracil (300 mg/m2/day). Surgical resection was performed in 36 patients with pathological assessment of tumor response and margins. Patients with sphincter-sparing resection and distal margins > 1 cm or < or = 1 cm and those who underwent APR were compared. RESULTS: Thirty-six patients completed preoperative chemoradiotherapy, with successful sphincter-preservation in 28 patients. At a median follow-up of 33 months, there were 12 recurrences overall, which included 11 distant failures and four pelvic failures. Disease-free survival (DFS) was not different between those who had an APR compared with sphincter-sparing resection with distal margins < or = 1 cm. DFS was worse (P < .02) when radial margins were < or = 3 mm compared with > 3 mm. CONCLUSIONS: Sphincter preservation is feasible in more than 75% of patients with tumors < or = 8 cm from the anal verge after preoperative chemoradiotherapy. Sphincter-sparing surgery with distal margins < or = 1 cm can be used without adversely influencing local recurrence or DFS. Limited radial margins (< or = 3 mm), however, are associated with increased disease recurrence.

Adenocarcinoma↗

[The psychology of compassion. An analysis of the 100th anniversary of the death of Fredrich Nietzsche].

Friedrich Nietzsche is supposed to have been one of the harshest critics of compassion. Many of his publications try to unmask its failings and to expose its true motives. From an ardent admirer of Schopenhauers's ethics of compassion, Nietzsche turned into a vigorous despiser of compassionate feelings. It is shown that this change was above all caused by overwhelming personal experiences of compassion due to illness and death in his family and, later on, with his first aid activities in military hospitals during the German-French war in 1870. Combined with that, Nietzsche suffered from feelings of passivity and helplessness, which gave him the impression of compassion being a negative and--in the end--loathed emotion.

Empathy↗

Primary extra-nodal lymphoma of the urinary bladder.

Primary non-Hodgkin's lymphoma of the urinary bladder is rare. Only a few cases have been reported. We report the case of a woman with non-Hodgkin's lymphoma of urinary bladder and review the literature.

Antigens, CD20↗

[Friedrich Nietzsche: history of his illness. On the 100th anniversary of the death of the poet-philosopher].

The philosopher Friedrich Nietzsche was one of the most famous patients in the psychiatric hospital Jena. Between 1889 and 1890, Otto Binswanger und Theodor Ziehen treated the progressive paralysis of Friedrich Nietzsche whose 100th anniversary of death is on 25th August 2000. After Nietzsche's death, an animated discussion about his disease arose. Many objected against the syphilitic diagnosis of the disease. Nietzsche's medical fill became a popular object of science, although it ended as a very odd story.

Famous Persons↗

[The young Heine. Case history of pseudologia phantastica].

The young Heinrich Heine showed signs of pseudologia phantastica. While studying the diaries of his greatuncle, he identified with the latter. The underlying factors of this psychopathological development are discussed in this paper.

Adolescent↗

[Comparison of WISC-R and Raven's Progressive Matrices tests in a clinical consultation population].

OBJECTIVES: What are the differences between measuring intelligence with the WISC-R or with the Progressive Matrices Tests? METHODS: 702 children were tested as outpatients of the Child and Adolescent Department of the Psychiatric University Hospital Erlangen-Nuremberg by means of the WISC-R and the Progressive Matrices Tests (CPM and SPM). RESULTS: Highly significant differences in the mean were found. The mean IQ was 10 points higher on the CPM than on the WISC-R but 6 points lower than the WISC-R on the SPM. At 0.67 the correlations between WISC-R and the Matrices Tests were each in the middle high range. Differences between the tests were substantial and remain unchanged despite the recently newly normed SPM.

Adolescent↗

Long-term occurrence of Trypanosoma congolense resistant to diminazene, isometamidium and homidium in cattle at Ghibe, Ethiopia.

Ten trypanosome isolates were collected at random from cattle at Ghibe, Ethiopia, in February 1993 and all shown to be savannah-type Trypanosoma congolense. When inoculated into naïve Boran (Bos indicus) calves, all 10 isolates were resistant to diminazene aceturate (Berenil), isometamidium chloride (Samorin) and homidium chloride (Novidium) at doses of 7.0 mg/kg body weight (b.w.), 0.5 mg/kg b.w. and 1.0 mg/kg b.w., respectively. In order to determine whether this multiple-drug resistance was expressed by individual trypanosomes, clones were derived from two of the isolates and characterised in mice for their sensitivity to the three compounds; by comparison to drug-sensitive populations, the two clones expressed high levels of resistance to all 3 trypanocides. In experiments to characterise the uptake kinetics of [14C]-Samorin, the maximal rates of uptake (Vmax) for 4 Ghibe isolates ranged from 9.2 to 15.0 ng/10(8) trypanosomes/min. In contrast, Vmax for the isometamidium-sensitive clone T. congolense IL 1180 was 86.7 +/- 8.6 ng/10(8) trypanosomes/min. Lastly, molecular karyotypes were determined for eight isolates: seven different chromosome profiles were observed. These data indicate that in February 1993 there was a high prevalence of drug-resistant trypanosome populations with different chromosome profiles in cattle at Ghibe. Since a similar situation existed at the same site in July 1989, this suggests that the drug-resistance phenotype of trypanosomes at Ghibe had not altered over a 4 year period.

Animals↗

[God is dead--Friedrich Nietzsche's Oedipus complex].

The early psychoanalysts were influenced by the philosophical ideas of FRIEDRICH NIETZSCHE. The work of SIGMUND FREUD was partly based on NIETZSCHE'S literary world. Just before his mental disaster NIETZSCHE radically destroyed once precious ideals. The roots of this provocative development will be elucidated by analyzing NIETZSCHE'S childhood. A main aspect is NIETZSCHES close mother-tie and especially his father's early death. The father-image of NIETZSCHE'S late years is an essential of this paper.

Famous Persons↗

Cytotoxicity, cellular accumulation and DNA binding of oxaliplatin isomers.

Oxaliplatin (trans-l-1,2-diaminocyclohexane oxalato Pt(II); 1R,2R-dach, l-OHP), its trans-d isomer (1S,2S-dach) and cis-dach (1R,2S-dach) isomers were compared in in vitro testing against human ovarian carcinoma cell lines A2780, A2780/CP (cisplatin resistant), A2780/l-OHP (oxaliplatin resistant), colon carcinoma cell line HT-29, and murine leukemia cell lines L1210, L1210/CP (cisplatin resistant), and L1210/dach (tetraplatin resistant). The relative molar potency of the three complexes in all the cell lines except A2780/l-OHP and L1210/dach are trans-l > trans-d > cis-dach; in A2780/l-OHP they are trans-l = trans-d > cis-dach; in L1210/dach trans-l > trans-d = cis-dach. The A2780/l-OHP selected for trans-l resistance is 3.6-fold resistant to oxaliplatin, showed no resistance to trans-d isomer and is 6-fold resistant to cis-dach. However, L1210/dach which is selected for carboxyphthalato 1,2-dach (trans-dl) platinum(II) is 140-fold resistant to oxaliplatin, 73-fold resistant to trans-d, and 41-fold resistant to cis-OHP. The accumulation and DNA binding of platinum following a 2-h treatment of A2780 cells with each of the isomers (60 microM) is in the order of trans-l > cis-dach > trans-d which corresponded to the cytotoxicity of trans-l, but not the others. The data suggest that other processes, such as differential formation of specific adducts and/or repair may be involved. Of the three isomers l-OHP is the superior and its accumulation and DNA binding are consistent with its cytotoxicity.

Animals↗

Role of target organ infection with cytomegalovirus in the pathogenesis of graft-versus-host disease.

Skin and rectal biopsy tissue from 34 allogeneic and 23 autologous BMT recipients was prospectively analysed for CMV using immunohistochemistry and PCR to investigate the hypothesis that target organ infection with CMV initiates and/or exacerbates GVHD. Biopsies were obtained prior to and at 3, 8 and 26 weeks after BMT and whenever GVHD was suspected. Surveillance specimens of peripheral blood leucocytes (PBL), urine and throat swabs were obtained every 2 weeks until 12 weeks after BMT, and whenever CMV was suspected. Cryostat sections were analysed immunohistochemically for CMV antigens and PBL and biopsies for CMV DNA by PCR. Of the 31 patients who engrafted, 28 (90%) developed GVHD clinically, confirmed histologically in 56 biopsies. GVHD proved clinically severe in 14 patients, 4 of whom had treatment-resistant GVHD. CMV was detected in PBL more frequently in patients with severe GVHD than in those with mild/moderate GVHD (29% vs. 7%). However, in all but one patient the onset of GVHD preceded detection of CMV. In biopsy specimens, CMV was detected in only 2 patients, 1 of whom had an exacerbation of GVHD temporally associated with CMV. Thus, despite a high incidence of GVHD in this series, with 56 episodes of GVHD in 28 patients, only 1 patient had CMV in biopsy tissue temporally associated with GVHD. This suggests that biopsy infection with CMV is not a major factor in initiating or exacerbating GVHD in this cohort. This study thus does not support a role for target organ infection with CMV in the pathogenesis of GVHD.

Adolescent↗

Human herpes virus-6 infection in marrow graft recipients: role in pathogenesis of graft-versus-host disease. Newcastle upon Tyne Bone Marrow Transport Group.

To investigate the hypothesis that target organ infection with human herpes virus-6 (HHV-6) exacerbates the clinical severity of GVHD, skin and rectal biopsies from 34 allogeneic bone marrow transplant (BMT) recipients and 23 comparative autologous recipients were studied. Biopsies and heparinised blood samples were obtained from all patients prior to and at regular intervals after BMT, and whenever GVHD was suspected. HHV-6 antigen was detected in cryostat sections by immunohistochemistry, and HHV-6 DNA in peripheral blood leucocytes (PBL) and biopsies by nested PCR. Twenty-eight (90%) of the 31 patients who engrafted developed clinical GVHD, which was mild in five, moderately severe in nine and severe in 14. Overall, HHV-6 DNA was detected in PBl in 74% of autologous recipients and 76% of allogeneic recipients, and in biopsy tissue in 48% of autos and 71% of allos. However, HHV-6 DNA was detected in skin and/or rectal biopsies more frequently in allogeneic recipients with severe GVHD (92%) than in those with either moderate (55%) or mild GVHD (22%), suggesting an association (P = 0.004) between HHV-6 DNA in biopsy tissue and GVHD severity. A significant linear trend (P = 0.03) was identified between detection of HHV-6 DNA in biopsy tissue obtained prior to or concomitant with the onset of GVHD and increased GVHD severity, suggesting that HHV-6 was causally linked to GVHD rather than reactivated as a consequence of GVHD therapy. Thus this study supports a role for HHV-6 in the initiation and/or exacerbation of GVHD, and suggests that the presence of HHV-6 DNA in the skin or rectum may be a factor in determining GVHD severity. If confirmed, these findings may have implications for the management of allogeneic BMT recipients.

Adolescent↗

MHC class II and ICAM-1 expression and lymphocyte subsets in transbronchial biopsies from lung transplant recipients.

The expression of MHC class II antigens and ICAM-1 and the composition of lymphocyte infiltrates have been studied in frozen sections of transbronchial biopsies from lung transplant recipients. First, biopsies obtained from patients who showed acute rejection, OB, and normal features were compared. Second, we compared first-year biopsies from patients developing OB and patients with a good clinical outcome. HLA-DR was widely expressed on epithelia and vascular endothelium. Increased vascular HLA-DP expression was found in OB biopsies. In OB patients there was a significantly increased frequency of bronchial HLA-DP and vascular HLA-DQ expression. Expression of ICAM-1 by bronchial and bronchiolar basal cells, a phenomenon not reported previously in humans, was seen in a small number of biopsies. CD8 predominant lymphocytic infiltrates were present in all groups and were increased in OB biopsies and OB patients. Increased numbers of CD4-positive cells were found in rejection and OB when compared with normal biopsies. These findings support an immunological basis for the development of OB.

Antigens, CD↗

Diagnostic features of transfusion associated graft versus host disease.

AIMS: To define the immunopathological profile of transfusion associated graft versus host disease (TA-GvHD) to elucidate its pathophysiology and to determine if any features are of diagnostic value. METHODS: Nine patients (age range 14-61 years) who developed histologically confirmed TA-GvHD between 1989 and 1992 were studied. Immunohistochemical analysis of frozen and formalin fixed skin biopsy tissue was performed. Sections were stained with antibodies to CD3, CD8, CD4 and HLA-DR, using a routine streptavidin-biotin technique with standard diaminobenzidine development. RESULTS: All biopsy specimens showed aberrant positive expression of HLA-DR by epidermal keratinocytes. In four patients, all of whom died, HLA-DR was diffusely expressed throughout the epidermis; in the other five cases keratinocyte expression of HLA-DR was more focal. In all biopsy specimens T cells had infiltrated the dermis and epidermis. In all nine cases CD4+ T helper/inducer cells were the predominant T cells. DISCUSSION: Immunohistochemical studies are of value in the diagnosis of TA-GvHD. Aberrant keratinocyte expression of HLA-DR and dermal and epidermal infiltration of CD4+ T cells are immunopathological features of TA-GvHD. Immunohistochemical analysis of skin biopsy tissue using antibodies to these markers is thus a useful investigation in pancytopenic patients presenting with unexplained rashes.

Adolescent↗

Constitutive expression of MHC and adhesion molecules by alveolar epithelial cells (type II pneumocytes) isolated from human lung and comparison with immunocytochemical findings.

Highly purified populations of alveolar epithelial cells (type II pneumocytes) were isolated from human lung specimens. These cells were characterised histochemically, by demonstrating the presence of intracellular alkaline phosphatase, and morphologically, by electron microscopic demonstration of lamellar bodies and microvilli. Expression of the epithelial glycoprotein HEA-125, of MHC class I and class II (HLA-DR, -DP and -DQ) antigens and of the intercellular adhesion molecules ICAM-1, VCAM-1, LFA-3 and B7 was quantified by flow cytometry. Comparison was made between the expression of these molecules by isolated type II cells and by alveolar epithelium in normal human lung tissue after immunocytochemical staining of frozen sections of donor lung. Isolated type II pneumocytes expressed HEA-125 and class I MHC molecules and the class II MHC molecules HLA-DR and -DP; HLA-DQ was not detected. The intercellular adhesion molecule ICAM-1 was expressed constitutively at low levels but there was minimal expression of VCAM-1, LFA-3 and B7. It was not possible to differentiate type II cells from the predominant type I pneumocytes on frozen sections. Alveolar epithelium expressed HEA-125, class I MHC antigens, the class II molecules HLA-DR, and -DP and the intercellular adhesion molecule LFA-3. Expression of the adhesion molecules ICAM-1, VCAM-1 and B7 was variable. As with the isolates, HLA-DQ was not observed on alveolar epithelium. In conclusion, a reproducible method for the isolation of pure populations of human type II pneumocytes has been developed. These cells were not damaged by the isolation procedure. It is not known whether alveolar epithelium can present antigens to T lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Late development of graft-versus-host disease in an autologous BMT recipient.

Clinical and histological changes consistent with GVHD have been described in recipients of both syngeneic and autologous grafts. The mechanism of autologous GVHD is well documented. However, cases of autologous GVHD previously reported have all occurred within the first 2 months post-BMT. We report the case of an autologous BMT recipient in whom histological features consistent with GVHD emerged 7 months post-BMT, which may have implications for the long-term follow-up of autologous marrow graft recipients.

Bone Marrow Transplantation↗

Differentiation of materno-fetal GVHD from Omenn's syndrome in pre-BMT patients with severe combined immunodeficiency.

Materno-fetal GVHD is commonly a fatal condition occurring in patients with severe combined immunodeficiency (SCID). Definitive diagnosis is often difficult. We describe a patient with clinical features suggestive of materno-fetal GVHD but in whom histology was atypical. Y chromosome-specific PCR amplification analysis of DNA extracted from the skin biopsy was performed to detect chimeric evidence of infiltrating maternal T cells. This revealed strong positivity for the Y chromosome, indicating lack of maternal T cell engraftment and thus confirming a diagnosis of Omenn's syndrome, a variant of SCID in which atypical lymphocyte clones give rise to a similar picture. In contrast, Y chromosome-specific PCR analysis of skin biopsy DNA from a male patient with a rash clinically and histologically typical of materno-fetal GVHD revealed absence of the Y chromosome, indicating infiltration of maternal cells and thus confirming the diagnosis of materno-fetal GVHD. Y chromosome-specific PCR analysis is thus a useful investigation for the differentiation of materno-fetal GVHD from Omenn's syndrome in pre-BMT SCID patients presenting with unexplained rash.

Bone Marrow Transplantation↗