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Biomedical subjects

H Kaufmann

Publications and source records attributed to H Kaufmann.

At least 37 records · Page 2Linked to original sources

Examination of young children with Lea symbols.

AIMS: In order to establish normal values and interocular differences of visual acuity, Lea symbols were applied to neurologically and ophthalmologically normal children. METHODS: 385 children (21-93 months old) were examined, within a routine check up in an urban paediatric practice where Lea symbol acuity (LS) was measured. Of these children, 90 were re-examined in hospital comparing Lea symbol acuity (LS) and Landolt C acuity (LC). Strabismus, ametropia, and any organic eye disease were excluded. RESULTS: In the paediatric practice, LS could be measured on both eyes in 54% of the children. In the age group above 36 and 48 months the success rate was 76% and 95%, respectively. Acuity in the paediatric practice ranged from 0.1 to 2.0 (median 1.25) in the whole group. Interocular acuity difference was one line or less in 80%. In the hospital, LS and LC could be measured on both eyes of 77% and 48% of the 90 children, respectively. Cooperation increased with age. LS in the hospital ranged from 0.32 to 2.0 (median 1.0) and LC from 0.16 to 1.25 (median 0.8). Interocular difference of LS acuity was one line or less in 90%. CONCLUSION: Lea symbols were found to be useful for visual acuity assessment in early childhood. Significant variability of visual acuity in this age group is caused by cooperation. When monocular measurements are possible on both eyes, however, the intraindividual interocular difference of visual acuity usually does not exceed one line.

Child, Preschool↗

High blood pressure and decreased heart rate variability in the Cuban epidemic neuropathy.

Autonomic cardiovascular reflexes were investigated in patients with an epidemic optic and peripheral neuropathy, which affected more than 50 000 people in Cuba between 1991 and 1994 and was probably caused by nutritional deficiency. Affected patients had significantly higher blood pressure than age matched controls, both while supine and standing, and significantly lower heart rate variability during paced breathing, suggesting reduced cardiac parasympathetic innervation.

Adult↗

Botulinum toxin type A in primary palmar hyperhidrosis: randomized, single-blind, two-dose study.

BACKGROUND: Primary palmar hyperhidrosis is characterized by excessive sweating due to increased sympathetic cholinergic sudomotor nerve traffic to the palmar surface of the hands. Clinical studies suggest that intradermal injections of botulinum toxin are effective in the treatment of palmar hyperhidrosis. OBJECTIVES: To establish the effectiveness of intradermal botulinum toxin in reducing hyperhidrosis, to determine the most effective dose of toxin, and to examine its effect on muscle strength. METHODS: In a prospective, single blind, randomized trial, 24 patients with severe palmar hyperhidrosis received either a low (50 U) or a high dose (100 U) of botulinum toxin type A (Botox, Allergan) injected intradermally in 20 sites in each palm. RESULTS: Following injection with either dose, iodine starch test revealed a significant decrease in sweating within the first month. Six months after injection, the anhidrotic effect was still evident in two thirds of the patients in both groups. Handgrip strength was not affected with either dose but finger pinch strength, 2 weeks after the injection, decreased 23 +/- 27% with 50 U (p < 0.05) and 40 +/- 21% with 100 U (p < 0.001). Pinch strength improved gradually but 6 months after treatment it was still 7-11% lower than at baseline. CONCLUSIONS: Both 50 and 100 U of botulinum toxin type A, injected intradermally in each hand, decreased sweating in patients with primary hyperhidrosis for at least 2 months in all the patients, and 6 months in most patients. Weakness in the intrinsic muscles of the hand was observed.

Adult↗

Characterization of an N-terminally truncated cyclin A isoform in mammalian cells.

Cyclin A is essential for regulating key transitions in the eukaryotic cell cycle including initiation of DNA replication and mitosis. This paper describes the characterization of a truncated cyclin A isoform (cyclin A(t)) in vitro in cultured mammalian cells and in mouse tissues. The presence of cyclin A(t) in specific cell types correlates with the ability of cell extracts to cleave in vitro translated cyclin A. In CHO-K1 cells, cyclin A processing to cyclin A(t) occurs at the N terminus; it does not involve the 26 S proteasome, nor could it be induced by conditional overexpression of the cyclin-dependent kinase inhibitor p27(Kip1). However, high cell densities lead to increased cyclin A(t) levels. Unlike full-length cyclin A, cyclin A(t) localizes to the cytoplasm, where it binds Cdk2. The data suggest that cyclin A processing occurs in vivo to yield an N-terminally truncated isoform by an unknown mechanism that is regulated by cell density. Differential subcellular localization may provide the first insights into the physiological role of cyclin A(t).

Animals↗

Comparative analysis of two controlled proliferation strategies regarding product quality, influence on tetracycline-regulated gene expression, and productivity.

Overexpression of the cyclin-dependent kinase inhibitor p27 and exposure to low temperature (30 degrees C) represent two strategies to establish controlled proliferation processes for production of therapeutic proteins using Chinese hamster ovary (CHO) cells. Here we analyze the effect of growth inhibition on the quality of the human model glycoprotein SEAP (secreted alkaline phosphatase) for both strategies in monoclonal CHO-derived cell lines. Separation of purified SEAP samples using two-dimensional gel electrophoresis showed that production by proliferation-controlled CHO cultures did not alter the overall integrity of the product. Further, oligosaccharide profiles were compared using HPEC-PAD analysis. No differences were detectable between SEAP profiles obtained from p27 growth-arrested and proliferating cultures. However, production at 30 degrees C led to a significant increase in the degree of sialylation, an effect that is generally considered beneficial for the in vivo efficacy of protein therapeutics. In the production context presented here, SEAP expression is controlled by the tetracycline- (tet) repressible gene regulation system. Here we show low temperature-induced upregulation of the tetracycline-dependent transactivator (tTA). This induction has been shown by Northern blot analysis to occur at the mRNA level and is independent of the promoters driving the transactivator. We also describe a novel bottleneck in productivity at low temperature found in p27 growth-arrested CHO cells cultivated at 30 degrees C.

Alkaline Phosphatase↗

Use of antibodies for detection of phosphorylated proteins separated by two-dimensional gel electrophoresis.

Protein phosphorylation and dephosphorylation are key regulatory mechanisms in prokaryotic and eukaryotic cells. Considering the role of phosphorylation in many human diseases, it appears a major challenge to refine on the methods to analyze the phospho-proteome. Here we review the use of monoclonal antibodies directed against specific phosphorylated amino acid residues to visualize phosphoproteins separated by two-dimensional gel electrophoresis. Strategies are described how this method can successfully be applied to create phospho-proteome maps of mammalian cells.

Animals↗

Why do we faint?

Explore the source record for details and available documents.

Blood Pressure↗

Autoregulatory cerebral vasodilation occurs during orthostatic hypotension in patients with primary autonomic failure.

It is unclear whether patients with autonomic failure autoregulate cerebral blood flow during hypotension. The objective in this study was to examine cerebral autoregulatory capacity in patients with autonomic failure by studying changes in middle cerebral artery blood flow velocity using transcranial Doppler ultrasonography before, during, and after tilt-induced hypotension. Nine patients with primary autonomic failure were evaluated. Mean arterial pressure and middle cerebral artery blood flow velocity were simultaneously recorded while the patients were in the supine position, during 60 degrees head-up tilt, and after they were returned to the horizontal position. The results were as follows: during tilt-induced hypotension, mean arterial pressure decreased significantly more than middle cerebral artery mean blood flow velocity (58% versus 36%, p <0.0002). After return to the horizontal position, mean arterial pressure returned to baseline, and middle cerebral artery blood flow velocity transiently increased above pretilt value (p <0.02). It is concluded that cerebral autoregulatory vasodilation occurs in patients with autonomic failure. This was demonstrated by a more pronounced decline in mean arterial pressure than in middle cerebral artery blood flow velocity during hypotension and by a transient increase in middle cerebral artery blood flow velocity (ie, hyperemic response) after blood pressure was restored.

Aged↗

Deletion of chromosome 13q14 detected by fluorescence in situ hybridization has prognostic impact on survival after high-dose therapy in patients with multiple myeloma.

Interphase cytogenetic analysis of chromosome 13q14 was performed in 28 patients with multiple myeloma (MM) receiving high-dose therapy followed by autologous (n=24) or allogeneic (n=4) stem cell support. Eleven (39%) patients were found to have a deletion of chromosome 13q14. Response rates to high-dose therapy were independent of the chromosome 13 status, but patients with a deletion of 13q14 had a significantly shorter progression-free (p=0.001) and overall survival (p=0.012) than patients with normal chromosome 13q14. Our results indicate that high-dose therapy appears promising in patients with normal chromosome 13, whereas in patients with a deletion of 13q14 innovative therapeutic concepts are warranted.

Actuarial Analysis↗

Absence of clonal chromosomal relationship between concomitant B-CLL and multiple myeloma--a report on two cases.

B-cell chronic lymphocytic leukemia (B-CLL) and multiple myeloma (MM) are chronic B-cell malignancies that represent different stages of B-cell maturation. Occasionally, both diseases are present in the same patient, and this raises the question of clonal associations between the two neoplasms. We here report on two patients with concomitant B-CLL and MM. Clonal chromosomal abnormalities in both lymphocytic cells and plasma cells were studied by interphase fluorescence in situ hybridization (FISH) using a panel of 24 chromosome- and region-specific DNA probes. In the first patient, cytogenetics revealed 47, X, t(Y;22)(p11;q10), +12, dell4(q21q32). By FISH, +12 was present in lymphoid cells, but not in plasma cells. MM cells were characterized by multiple chromosomal gains (1, 11q23) and losses (5q, 10, 13q14, 15, 17p13, Y), which were all undetectable in lymphoid cells. The second patient, in whom no clonal abnormalities were obtained by conventional cytogenetic analysis, had lymphoid cells with loss of 8q24 by FISH. In contrast, evidence for a gain of 8q24 (consistent with amplification of c-myc) was obtained in 13% of plasma cells. Plasma cells were further characterized by gains of chromosomes 1, 3, 11, 18, and Y. We thus conclude that this comprehensive molecular cytogenetic analysis demonstrates the existence of two clonally distinct B-cell malignancies in both patients.

Aged↗

Advances in the biology and therapeutic management of multiple myeloma.

During the past decade, new developments have increased our understanding of the biological features of multiple myeloma (MM), and novel therapeutic approaches have improved the outcome and quality of life. The importance of both the malignant clone and the bone marrow environment for disease evolution and propagation has been recognized, and therapeutic approaches that target both components of the disease process appear to be most promising. Along this line, thalidomide has been observed to exert activity in chemotherapy-refractory MM and thus expands the therapeutic armamentarium against MM. Use of high-dose melphalan with autologous stem cell transplantation has resulted in an improved rate of complete remissions as well as prolonged event-free and overall survival. Novel treatment strategies exploiting anti-myeloma immunity (nonmyeloablative allogeneic transplantation, vaccination) are being investigated and carry the potential to further improve the outcome of patients with MM.

Humans↗

Surgery for nystagmus related head turn: Kestenbaum procedure and artificial divergence.

PURPOSE: An abnormal head posture adopted to reduce a nystagmus can be treated by Kestenbaum surgery or by creating an exodeviation which is compensated by convergence (artificial divergence). We evaluated the effects of Kestenbaum surgery and artificial divergence surgery in a retrospective study. METHODS: Seventy-eight patients who received surgery for horizontal head turn (HT) due to nystagmus were included in the study. Exclusion criteria were previous extraocular muscle surgery, strabismus, lack of binocular vision, and cerebral disease. The millimetres of surgery and the findings before and 3 months after operation [HT, binocular visual acuity (VA), binocular vision (BV)] were evaluated. The patients were divided into three groups: the Kestenbaum group, the artificial divergence group, and the artificial divergence plus Kestenbaum group. RESULTS: Of the 78 patients, aged 3-68 years, 52 had HT to the left side and 47 were male. In the Kestenbaum group (n=31), the median (10% and 90% quantile) HT was 30 degrees (range 20-40 degrees). A total of 28 mm (range 20-40 mm) surgery reduced the HT to 10 degrees (0-30 degrees). The efficacy of surgery was 1.4 degrees HT reduction per millimetre surgery on one eye (range 0.4-2.5 degrees). Four patients received further surgery. In the artificial divergence group (n=27), 10 mm (range 7-12 mm) surgery reduced the HT of 30 degrees (range 25-40 degrees) to 5 degrees (range 0-20 degrees). Seven patients received further surgery. In the artificial divergence plus Kestenbaum group (n=20), the HT was 30 degrees (range 25-40 degrees). A total of 29 mm (range 21-37 mm) surgery reduced the HT to 7 degrees (range -5 degrees to 15 degrees). No further surgery was performed. Postoperatively, the maximum VA and BV was available without large HT, but an increase in the absolute VA and BV could not be proved. CONCLUSION: Artificial divergence is preferable or should be combined with Kestenbaum surgery, if possible. Kestenbaum surgery alone has an effect/dose ratio similar to recess-resect surgery for strabismus. Thus, to correct x degrees HT, 2/3x mm surgery on each eye is adequate.

Adolescent↗

[Results of combined divergence operation in intermittent exotropia in 120 children].

BACKGROUND: Intermittent exotropia is the most frequent indication for surgical correction of exodeviations in childhood. Overcorrection with prolongated or persistent consecutive esotropia can impair binocular vision particularly in early childhood. We wanted to investigate this potential risk and the dose/effect relation of recess-resect surgery on children. PATIENTS AND METHODS: 120 children up to ten years of age underwent recess-resect surgery for intermittent exotropia in our clinic from 1991 to 1999 (< 2% of the surgical cases). The cycloplegic refraction was spectacle corrected with a reduction of 0.5 dpt. Preoperatively, a diagnostic occlusion was performed for three days. The amount of surgery was calculated using our dosage schedules based on effects one week postoperatively. The squint angles as measured by the alternate prism and cover test at 5 m and 0.3 m pre- and 3 months postoperatively and the binocular functions as measured by the Bagolini striated glasses, Titmus, Randot, TNO, or Lang tests were evaluated. RESULTS: (Medians) Squint angles in primary position were: preoperative: distance (5 m)--15 degrees, near (0.3 m)--16 degrees; postoperative (n = 104); distance--4 degrees, near--3 degrees. Effectivity of surgery: distance: 1.3 degrees/mm, near 1.4 degrees/mm. Consecutive esotropia requiring surgical correction occurred in 1 child. Second surgery for intermittent exotropia in the years 1991 to 1999 was necessary in 5 children. Binocular functions (n = 95): Preoperative = postoperative: 61%, postoperative > preoperative 21%, postoperative < preoperative 18%. The diagnostic occlusion was helpful to differentiate "pseudo-divergence excess type" from "divergence excess type" exotropia. The average deviation did not increase under the diagnostic occlusion. The effectivity of surgery (degree/mm) in the children group was lower than in a compared group of older patients (> 10 years) with intermittent exotropia. CONCLUSION: Using our own dosage schedules and surgical technique, residual exodeviations are common after recess-resect surgery in childhood. The risk of consecutive esotropia or persistent impairment of binocular vision is low.

Child↗

[Unilateral aplasia of a lateral rectus muscle].

BACKGROUND: The congenital absence of an extraocular muscle is rare. The case of an unilateral lateral rectus muscle and a review of the literature are presented. PATIENT AND METHODS: A healthy 7-year old boy with inconspicuous family history was seen in our clinic. The boy had been noted to have a right esotropia from infancy. Clinical orthoptical examinations and magnetic resonance imaging (MRI) were performed. The esotropia was corrected by transposition of the superior and inferior rectus muscle. RESULTS: With correction of the myopic astigmatism the visual acuity of either eye was 0.8. The right eye could not abduct to pass the midline, the left eye passed the midline by 35 degrees. From the primary position the right eye was able to elevate by 20 degrees and the left eye to elevate 15 degrees. The alternate prism and cover test showed in either eye fixation an esotropia of 24 degrees without significant change in elevation or depression. Besides, there was a hypertropia (+VD) of 14 degrees which increased to 21 degrees in left gaze and decreased to 0 degree in right gaze. Indirect ophthalmoscopy showed a bilateral excyclo position of approximately 5-10 degrees. Retraction of either eye was not seen in any gaze direction. The axial length of the right/left eye was 25.2 mm/24.6 mm. Aplasia of the right lateral rectus muscle and hypoplasia of the left lateral rectus muscle could be demonstrated by magnetic resonance imaging. Intraoperatively the right lateral rectus muscle was absent. The vertical eye muscle inserted regularly. Hummelsheim's procedure was performed. Eight months postoperatively, the boy was orthotropic in primary position. The inferior oblique overaction was still present together with a "V" pattern of 8 degrees. The Bagolini test was positive. CONCLUSION: The congenital absence of one or more extraocular muscles is a rare condition, which has to be considered as a differential diagnosis to neurogenic nerve palsy.

Child↗

Binocular 3-D video-oculography.

A video technique is described to record ocular motions and positions of both eyes simultaneously in all degrees of freedom. This non-invasive method allows a 3-D positional analysis with free gaze directions and head tilts for measuring all ocular degrees of freedom, including torsion.

Diagnostic Techniques, Ophthalmological↗

Design of a novel mammalian screening system for the detection of bioavailable, non-cytotoxic streptogramin antibiotics.

Screening and development of new antibiotic activities to counteract the increasing prevalence of multidrug-resistant (MDR) human pathogenic bacteria has once again become a priority in human chemotherapy. Here we describe a novel mammalian cell culture-based screening platform for the detection of streptogramin antibiotics. Quinupristin-dalfopristin (Synercid), a synthetically modified streptogramin, is presently the sole effective agent in the treatment of some MDR nosocomial infections. A Streptomyces coelicolor transcriptional regulator (Pip) has been adapted to modulate reporter gene expression (SEAP, secreted alkaline phosphatase) in Chinese hamster ovary cells (CHO) in response to streptogramin antibiotics. This CHO cell-based technology was more sensitive in detecting the production of the model streptogramin pristinamycin, from Streptomyces pristinaespiralis, than antibiogram tests using a variety of human pathogenic bacteria as indicator strains. The reporter system was able to detect pristinamycin compound produced by a single S. pristinaespiralis colony. The assay was rapid (17 hours) and could be carried out in a high-throughput 96-well plate assay format or a 24-well transwell set-up. This novel mammalian cell-based antibiotic screening concept enables detection of bioavailable and non-cytotoxic representatives of a particular class of antibiotics in a single assay and represents a promising alternative to traditional antibiogram-based screening programs.

Alkaline Phosphatase↗