[Between "folk medicine" and "naturopathy": Zurich medical alternatives].
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History, 20th Century↗
Biomedical subjects
E Wolff
Publications and source records attributed to E Wolff.
Enalapril and prednisone in children with nephrotic-range proteinuria.
The effect of enalapril and low prednisone doses on the urinary protein electrophoretic pattern was studied in 13 pediatric patients with glomerular diseases and steroid-resistant nephrotic syndrome. Enalapril was administered at doses of 0.2-0.6 mg/kg per day for 24-84 months, and prednisone was introduced 2 months later in 11 patients at doses of 30 mg/m2 on alternate days. The urine protein electrophoretic pattern showed a reduction of 80% and 70% in the total protein and albumin, respectively, after enalapril. Total urinary protein decreased from 5.46 to 1.1 g/m2 per day (P<0.001). A marked change from a pattern of non-selective urinary protein loss to an albumin-selective proteinuria was observed. Mean total plasma proteins increased from 4.7 to 5.43 g/dl (P<0.001). Four patients became free of proteinuria 24 months after enalapril was started, but only 2 remained free of proteinuria at 48 months of follow-up. The other 11 patients had persistent albuminuria of between 0.5 and 2.6 g/m2 per day with a selective urinary electrophoretic pattern. No additional decrease was observed after steroids were introduced. A clinical improvement in edema was observed in all children. Three patients developed transient acute renal failure, during the course of an infectious disease; 2 developed peritonitis and 1 pneumopathy. In these patients withdrawal of enalapril was necessary until a complete recovery of renal function was observed. Four patients were hypertensive on admission, achieving normal blood pressure 1 month after enalapril was started. No episodes of systemic arterial hypotension were seen. Creatinine clearance and serum potassium showed no statistically significant change.
Angiotensin-Converting Enzyme Inhibitors↗
Prevalence of factor V Leiden mutation in young adults with cerebral ischaemia: a case-control study on 225 patients.
Cerebral ischaemia in young adults is a well-recognised disease, and approximately half of the cases remain aetiologically unclear despite extensive investigations. Thrombophilias are known to cause a subset of ischaemic strokes in this population. The factor V Leiden (FVL) mutation, causing resistance to activated protein C, has recently been recognised as the most important genetic thrombophilia in the Western population. Carriers of this gene mutation have a sevenfold increased risk of phlebothrombosis. We undertook this study to evaluate whether the FVL mutation constitutes a risk factor for juvenile cerebral ischaemias. A total of 225 patients aged < or = 45 years at onset of cerebral ischaemia and 200 age-matched healthy controls were investigated. The overall frequency of heterozygosity for the FVL mutation did not differ significantly between patients (8.4%) and controls [6.0%; odds ratio (OR) 1.4, 95% confidence interval (CI) 0.7-3.1]. In the subgroup of patients with cryptogenic cerebral ischaemia (n = 94), however, a significantly higher frequency of this gene defect (15.9%) was found compared with the controls (OR 3.0, CI 1.3-6.6). Further trends towards higher frequencies of the FVL mutation were found in patients with patent foramen ovale (OR 1.9), individual (OR 2.1) or family history of previous thrombembolisms (OR 2.0), and in those aged 25 years at onset of disease (OR 1.9, all not significant). In conclusion, the FVL mutation is not a risk factor for cerebral ischaemia of the young. However, our results suggest that this gene mutation plays an aetiological role in the subgroup of patients suffering from 'cryptogenic' ischaemic events.
Adolescent↗
Oral squamous cell carcinomas are characterized by a rather uniform pattern of genomic imbalances detected by comparative genomic hybridisation.
Total genomic DNA sampled from 20 oral squamous cell carcinomas (SCCs) and from four SCC cell lines, was examined for genomic imbalances using comparative genomic hybridisation (CGH). Gains and losses of DNA copy number aberrations (CNAs) were found in the primary tumours, but also in the cell lines at a varying number. The patterns of CNAs proved to be rather peculiar in oral SCCs, gains of genetic material clearly dominating compared with losses, and a rather high uniformity of these patterns was an impressive finding. Hypersomies of whole chromosomes, e.g. numbers 17 and 19 or of whole chromosome arms, e.g. 20q, were particularly evident. The segments most frequently gained in oral SCCs were 3q26-q27, 5p15 and 9q34 (16 of 20 tumours each), as well as 1p36.3, 8q24, 10q26, 19 and 20q (15/20 each). Among the 15 tumours with more than 10 CNAs, all showed these imbalances. 11q13 was a band often involved in increases (14/20 tumours), but in several tumours was involved in amplification of DNA copy number. Several other chromosomal segments over represented in more than 60% of the tumours, as, for example, 12q24, 15q22-q24, 16p13.2 and 17q (14/20 tumours each), 6q26-qter, 7p22, 12p12.2-p13, 14q31-q32.2 (13/20) and 1q32-q41, 2q37, 16q23-q24 (12/20 each). In contrast, loss of material affected only a few chromosomal segments, as, for example, 3p12 (12 of the 20 tumours), 5q21 (10/20), 6q13 (8/20). The peculiarities of these findings, in some respect, differ from those found in other epithelial tumours, suggesting a high impact of environmental factors in the generation and progression of these tumours.
Adult↗
Factor V Leiden mutation is a risk factor for cerebral venous thrombosis: a case-control study of 55 patients.
BACKGROUND AND PURPOSE: Different coagulation disorders have been associated with cerebral venous thrombosis (CVT). Until now, fewer than 50 patients have been reported with CVT and the factor V Leiden (FVL) mutation. Although the prevalence of FVL-positive patients with CVT ranged from 10% to 25%, it was as low as 0.5% to 3% in the control groups. Most other studies had not systematically searched for concomitant risk factors or previous thromboembolic events. To better define the relevance of the FVL mutation in conjunction with additional risk factors in CVT, we conducted the present case-control study. METHODS: Fifty-five patients with CVT were compared with 272 healthy controls. A standardized interview regarding established risk factors for venous thrombosis and the patients' and their families' histories for thromboembolic events was performed. The presence of the FVL mutation was determined by polymerase chain reaction on DNA obtained from peripheral blood leukocytes. RESULTS: Of 55 patients, 8 (14.5%) were heterozygous for the FVL mutation compared with 17 of 272 controls (6.25%). The relative risk for the presence of FVL was 2.55 (95% confidence interval, 1.04 to 6.26; P=0.04). Additional risk factors for CVT were frequently found in both the presence and absence of FVL. Recurrence of venous thromboembolic events was more frequent in patients with the FVL mutation (5 of 8 patients, 62.5%) than in those without this anomaly (8 of 47 patients, 17%; P<0.005). CONCLUSIONS: Our study confirms the FVL mutation as the most relevant hereditary risk factor for CVT. Coexisting risk factors are usually involved in the initiation of CVT. Patients with the FVL mutation are at an increased risk for recurrent venous thrombosis.
Adolescent↗
Perspectives on patients' history: methodological considerations on the example of recent German-speaking literature.
Patient-history is a recently developed branch of medical-historical search, and its methodology has not yet been sufficiently developed. In particular, the specific character of patient-centered research still has not received sufficient attention. What kinds of questions can, and should, such research attempt to answer, and from which perspectives? This contribution to the discussion offers some help towards the development of ways of orienting such research towards achieving proximity to the patients' viewpoint. This aim is best achieved when the mental picture of patients is reconstructed and, in addition, the specific point of view of the patient is adopted. The article illustrates some possibilities and problems of this branch of research by citing the example of relevant recent German-language studies, especially in the field of the relationship of patients to approved doctors in the nineteenth century.
Germany↗
Gain of DNA copy number on chromosomes 3q26-qter and 5p14-pter is a frequent finding in head and neck squamous cell carcinomas.
Comparative genomic hybridization (CGH) was used to study genomic imbalances in 77 squamous cell carcinomas of the head and neck (HNSCC) and in four cell lines derived from oral carcinomas. Particular attention was paid to all tumors characterized by a gain of two specific chromosomal segments, i.e. 3q26-qter and 5p14-p15. The 57 tumors containing both or one of the two imbalances were compared with 20 tumors lacking both with regard to genomic complexity, as well as to associated genomic, histopathologic and clinical peculiarities. 60% of the oral, and 66% of the non-oral cancers exhibited a gain of 3q26-qter, while a gain of 5p14-p15 was found in 66% of the oral, but only in 48% of the non-oral tumors. 48% of all tumors were characterized by both gains together, 26% exhibited only one of the two alterations. It could be shown that presence of both, gain of 3q26-qter and 5p14-p15, was clearly associated with a significantly higher complexity of genomic changes which was not only expressed as a high frequency of DNA copy number alterations (CNAs) but was also connected with a considerable number of additional amplifications of various chromosomal segments and a high conformity of the patterns of genomic imbalances in these tumors. Clear differences of the extent and of the patterns of genomic imbalance could be observed between oral and non-oral tumors. With respect to histopathological parameters, no clear association could be found for specific imbalances to the grade of differentiation, nor the invasiveness or metastatic status of the tumors. However, a higher number of patients with tumors characterized by gain of 3q26-qter plus 5p14-p15 died within a short period (i.e. less than 15 months) after excision of the tumor compared to the group without these imbalances. The implications of these findings are discussed from the oncogenetic and clinical aspects and in comparison with other reports.
Journal Article↗
Pattern of genomic imbalances in oral squamous cell carcinomas with and without an increased copy number of 11q13.
Among 23 squamous cell carcinomas (SCC) of the oral cavity which were screened for DNA copy number alterations (CNAs) using comparative genomic hybridization, 14 showed a gain of, and 5 of these 14 even an amplification of band 11q13. Amplification of 11q13 was also detected in three of the four studied SCC cell lines and was confirmed by interphase FISH. The number of CNAs in addition to 11q13 varied from 14 to 47 in these carcinomas. All these tumors had seven other specific CNAs in common, i.e. gain on 1p36.3-36.6, 5p15, 9q34, 12p12-13, 14q32, 19 and 20q, all but one showed also an increase of copy number in 7p22, 8q24, 10q26, 12q26, 15q24-25, 16p, 16q23-24, 17q and 22q12-qter. These imbalances were distinctly rarer in the tumors without CNA in 11q13. Loss of material apparently played a minor role in these tumors with gain of 11q13, the most frequent losses (3p12-14 and 5q21) being present in 10 of the 14 cases and loss of 9p13-21 in 5/14 tumors. The three tumors with the highest number of CNAs in addition to 11q13, were histologically classified as pT4, three of the five tumors with 11q13 amplification were highly node-positive (pN 2b-2c). Two of the pT4 tumors shared as many as 23 specific chromosomal segments affected by CNA. Thus, gain of 11q13, though being found at different stages of karyotypic evolution, is apparently associated with a rather specific pattern of other CNAs and involved in progressed stages of malignancy in oral squamous cell carcinoma. In addition, the proportion of patients deceased within one year after diagnosis was clearly higher in the group whose tumors showed an increased 11q13 copy number as compared to the group without this increase. This could point to an association of gain in 11q13 and aggressiveness of the respective tumor.
Aged↗
[Anti-semitism in medicine and Jewish emancipation - the quarrel between the Gottingen obstetrician Friedrich Benjamin Osiander and his Jewish former student Joseph Jacob Gumprecht (circa 1800)].
This article analyzes the behavior of the renowned professor of obstetrics Friedrich Osiander towards his Jewish former student, the private lecturer Joseph Jacob Gumprecht. In a public academic debate between the two of them, Osiander made use of anti-Semitic arguments. He did so even though his medical ideas and practice were based on concepts of Enlightenment and especially religious tolerance. An analysis of Osiander's behavior shows that his denunciations were hardly emotional outbursts against Gumprecht. Rather, they were sober pedagogic attempts to cleanse Gumprecht from what Osiander saw as his "Jewishness", thereby helping him on his climb into bourgeois academic society. This interpretation fits well with the German "etatistic" version of Jewish emancipation: Jews were able to gain equal standing, but only under the condition of moral "improvement", or ridding themselves of all "Jewish attitudes." Thus, "Enlightened" ideas of Jewish emancipation were partly based on beliefs in Jewish moral inferiority. It is significant that the example under investigation happened in a medical faculty, since this was a prime location for acculturated Jews to meet Gentile scholars who represented the Enlightenment-influenced ideas of the times.
Germany↗
[Chronic hemodialysis in children].
BACKGROUND: The final objective of every children that is admitted to a program o hemodialysis of peritoneodialysis is to receive a renal graft. AIM: To report the experience in pediatric hemodialysis in two pediatric hospitals in Chile that are reference centers for renal transplantation. PATIENTS AND METHODS: Sixty patients, 55% female, aged 2 to 15 years old, admitted to the dialysis and transplant program since 1987, with a creatinine clearance of less than 20 ml/min/1.73 m2, were studied. RESULTS: Twenty percent of children were less than 5 years old at the moment of admittance to the program and 3.3% weighed less that 10 kg. Etiologies of end stage renal disease were glomerulopathies in 33.4%, reflux nephropathy in 27.7%, obstructive uropathy in 13.3%, hypoplasia/dysplasia in 10%, hereditary problems in 8.3% and vascular disorders in 5%. Eighty six percent of patients were dialyzed less than 2 years and 5% more than 4 years. Fifty percent had received prior medical treatment, 5% had been treated with intermittent peritoneal dialysis, 5% with chronic ambulatory peritoneal dialysis and 20% presented as a terminal renal failure. Sixty two percent received a renal graft, 25% is still on hemodialysis, 3.3% switched to chronic ambulatory peritoneal dialysis, 3.3% had a recovery of renal function and 6.7% died being on hemodialysis. Arterio-venous fistulae were the vascular accesses in 75% of patients, double lumen catheters in 50% and vein grafts in 5%. Malfunctioning or infections were the main complications of arterio-venous fistulae, accounting for 30% of hospital admissions. CONCLUSIONS: The availability of new vascular accesses and new hemodialysis machines specially designed for children, along with specially trained health care personnel, should reduce the mortality and complication rates of hemodialysis in this age group.
Adolescent↗
Plasminogen activator inhibitor-1 4G/4G-genotype is associated with cerebral sinus thrombosis in factor V Leiden carriers.
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Adolescent↗
[Long-term outcome of sex reassignment of male transsexual patients].
We report on our experience and our results with gender reassignment during the past 20 years. This study investigates the cosmetic and functional adequacy of the neovagina and also the psychological and social status in 37 surgically reassigned male-to-female transsexuals after a mean postsurgical follow-up of 7.5 years. There were 169 subjects who desired operations to adjust sex. In 58 cases the diagnosis "transsexualism" was supported by two psychosomatic and psychiatric expert opinions. We carried out 52 such operations in two stages. The mean age of the patients was 29 (18-40) years. The depth of the neovagina was approximately 12 cm, a cosmetic and physiologic result which adds greatly to the patients' satisfaction. There were no complications such as rectal or urethral fistulas. In one patient, vaginal stenosis developed after reoperation at a different institution. Three patients complained about short vaginas (6-9 cm). Correspondingly, the psychosocial status showed good improvement after surgery.
Adolescent↗
dpa, a member of the MCM family, is required for mitotic DNA replication but not endoreplication in Drosophila.
We have isolated the Drosophila disc proliferation abnormal (dpa) gene, a member of the MCM family of DNA replication factors. Members of this family of proteins are required for DNA replication in yeast. A dpa null mutant dies during pupal stages because imaginal tissues necessary for the formation of the adult fly fail to proliferate normally. Beginning in late embryogenesis BrdU labeling reveals DNA replication defects in mitotically proliferating cells. In contrast, dpa is dispensable for endoreplication, a specialized cell cycle consisting of consecutive rounds of S phases without intervening mitosis. Our studies suggest an essential role for dpa in mitotic DNA replication but not in endoreplication. Thus, dpa is not a general replication factor but may play a specialized regulatory role in DNA replication.
Amino Acid Sequence↗
The human high mobility group (HMG)-box transcription factor TCF-1: novel isoforms due to alternative splicing and usage of a new exon IXA.
The C-terminal peptide sequences of the human lymphocyte-specific high mobility group (HMG)-box transcription factor TCF-1 are determined by alternative splice mechanisms affecting the exons VIII to X. Here we report, in addition to four splice forms described previously (TCF-1A, B, C, D), the identification of three novel transcripts designated TCF-1E, F, G. Cloning and sequencing of the novel cDNAs revealed (i) joining of the exons VIII and IX to an internal exon X splice acceptor site resulting in a new open reading frame (ORF) of 99 amino acids derived from exon X sequences, (ii) the identification of an additional functional splice acceptor site within exon X, and (iii) a new 81-nucleotide insertion between exon VIII and exon X sequences in a novel transcript form. Genomic cloning and sequence analysis of this transcribed segment of 81 basepairs revealed that it was bordered by canonical splice consensus sites and located in a distance of some 400 bp from both the exons IX and X. It was therefore termed exon IXA. Novel ORFs were generated as a consequence of these alternative splice mechanisms resulting in TCF-1 gene products with significantly different C-terminal peptide sequences, which are prone to selective protein-protein interactions or transactivating functions.
Alternative Splicing↗
Calcitriol oral pulse therapy in children with renal osteodystrophy.
A 6-month protocol of oral pulse calcitriol was used in nine uraemic children (2-14 years old) on dialysis who presented with renal osteodystrophy. Calcitriol was administered twice a week, 4 micrograms per dose for patients over 30 kg and 3 micrograms for patients less than 30 kg. Plasma levels of parathyroid hormone, calcium, phosphorus and alkaline phosphatase were carefully controlled during the study. Parathyroid hormone levels decreased by 68% and 56% by the 2nd and 6th months of treatment in seven patients, while they remained unchanged in two patients with focal segmental glomerulosclerosis and massive proteinuria. Eight hypercalcaemic episodes from 77 determinations were observed, all of them recovered after 1 week of vitamin D withdrawal. We conclude that oral calcitriol pulse therapy is a good alternative for renal osteodystrophy in uraemic children. Careful monitoring of plasma parathyroid hormone and calcium is needed during follow-up when using this approach in paediatric patients.
Administration, Oral↗
In vitro and in vivo characterization of BR96 sFv-PE40. A single-chain immunotoxin fusion protein that cures human breast carcinoma xenografts in athymic mice and rats.
BR96 sFv-PE40 is a single-chain immunotoxin fusion protein targeted to the Ley Ag, which is expressed in many different human carcinomas as well as in normal gastrointestinal epithelium of humans and certain animals, including athymic rats but not mice. In vitro binding analysis determined that BR96 sFv-PE40 was similar in affinity to BR96 Fab. BR96 sFv-PE40 internalizes rapidly, similar to BR96 IgG. H3396 cells, derived from metastatic human breast carcinoma, have been established as tumor xenografts in estradiol-supplemented athymic mice and rats. H3396 tumor xenografts established in athymic mice (up to 350 mm3) and rats (up to 100 mm3) completely regressed after i.v. administration of BR96 sFv-PE40, given as 0.625 mg/kg (1.975 mg/m2) every 4th day for a total of five doses (mice) or 0.25 mg/kg (1.475 mg/m2) every 4th day for a total of four doses (rats). The tumors remained regressed for the duration of the study (> 85 days post-implant), which represents > 10 doubling times, indicating that the animals were cured. There was no toxicity in rats receiving a curative dose of 0.25 mg/kg, although liver and lung toxicity could be detected at a 16 times higher dose, 4 mg/kg or 23.6 mg/m2. We conclude, therefore, that BR96 sFv-PE40 can cure tumor xenografts at well tolerated doses and also in the presence of Ley expression in normal tissues.
ADP Ribose Transferases↗
Focal segmental glomerulosclerosis relapse after transplantation: treatment with high cyclosporine doses and a short plasmaphaeresis course.
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Child↗