Biomedical subjects
S Schulze
Publications and source records attributed to S Schulze.
T-cell-depleted peripheral blood stem cell transplantation for alpha-mannosidosis.
Alpha-mannosidosis (alpha-mannosidosis) is a lysosomal storage disease characterized by accumulation of oligosaccharides in various tissues leading to symptoms such as coarse facial features, dysostosis multiplex, hearing disabilities, mental developmental delay and skeletal involvement (dysostosis multiplex). Without treatment, the severe infantile onset form of this autosomal recessive disease leads to progressive neurodegeneration and sometimes to early death. Stem cell transplantation has been shown to be an effective treatment. In the five patients published so far, correction of skeletal abnormalities and improvement of neuropsychological capabilities have been observed. We report the first patient who received a T-cell-depleted peripheral blood stem cell transplantation (PBSCT) for alpha-mannosidosis. The diagnosis of alpha-mannosidosis was made at the age of 14 months. At the age of 24 months, he underwent PBSCT with T-cell depletion by CD34-positive selection from his HLA phenotypically identical mother. Conditioning was carried out with busulfan (20 mg/kg), cyclophosphamide (200 mg/kg), OKT3 and methylprednisolone. The patient is alive and well 27 months after PBSCT and has made significant developmental progress. The pattern of urinary oligosaccharides has returned to almost normal. CD34-positive-selected PBSCT is a feasible option to reduce risk for GVHD for these patients.
[Evaluation of Doppler sonographic criteria for the differentiation of hepatocellular carcinomas and regenerative nodules in patients with liver cirrhosis].
AIM: In order to improve the differentiation between hepatocellular carcinomas and regenerative nodules in patients with liver cirrhosis, Doppler-sonographic criteria for the tumours were evaluated. METHOD: Patients with histologically proven hepatocellular carcinoma (n = 35) and regenerative nodules (n = 10) were investigated by B-mode sonography as well as fundamental and echo-enhanced power-Doppler sonography focusing on specific properties of the tumours. The results were correlated to the histological findings. RESULTS: Hepatocellular carcinomas and regenerative nodules showed a different contrast behaviour with echo-enhanced power-Doppler sonography. The following features of hepatocellular carcinomas were frequently found: peritumoural signal detection in the early arterial phase, chaotic and centripetal contrast enhancement in the arterial phase, hypervascularization in the capillary phase, and loss of portalvenous blood flow. CONCLUSION: Hepatocellular carcinomas and regenerative nodules display different vascularization patterns in the echo-enhanced power-Doppler sonography. These characteristics can be useful for their differential diagnosis.
Endoscopic retrograde cholangiopancreatography causes reduced myocardial blood flow.
BACKGROUND AND STUDY AIMS: Previous studies have shown that up to 50% of healthy patients may develop ST-segment changes during upper gastrointestinal endoscopy. The aim of the study was to evaluate myocardial blood flow in patients during endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS AND METHODS: 11 patients scheduled for ERCP were monitored with a Holter tape recorder and underwent myocardial perfusion scintigraphies, to evaluate myocardial perfusion at rest and during ERCP. RESULTS: Ten patients completed the study. Eight patients had no sign of myocardial ischemia with either of the two methods, while two patients developed signs of ischemia during ERCP with both the Holter tape recording and on myocardial scintigraphy (P = 0.02). CONCLUSIONS: Patients undergoing ERCP may develop true myocardial ischemia with reduced myocardial blood flow. Although this is a small-scale study, these findings strongly support the use of alternative methods for diagnostic evaluation of the pancreatic duct and biliary tree.
[Laparoscopic cholecystectomy in outpatient surgery].
INTRODUCTION: The aim of the study was to describe the organisation of laparoscopic cholecystectomy in outpatient surgery and to discuss whether the method should be the future treatment of choice. MATERIAL AND METHODS: A retrospective descriptive study was carried out on 133 consecutive patients in the period 1 October 1999 to 30 September 2000. RESULTS: Seventy-seven per cent of the patients were discharged directly from the Department of Outpatient Surgery and 121 (97%) who underwent laparoscopy were discharged within 23 hours of the operation. The postoperative complication rate was 1.5% and the frequency of readmittance was 5%. DISCUSSION: Laparoscopic cholecystectomy is suitable for outpatient surgery and appears to be a recommendable setting for this operation. The method is safe and associated with few complications and readmittances.
Sealing of cystic duct with bipolar electrocoagulation.
BACKGROUND: The cystic duct leakage rate is still high. The aim of this study was to evaluate an alternative technique for securing the cystic duct using the Ligasure vessel sealing system. METHODS: Eight pigs were included in this pilot study. We performed a cholecystectomy, using the Ligasure system to sealing the cystic duct and artery. The pigs were killed 8 days after operation, and specimens of the cystic duct and common bile duct were removed for pathologic examination. RESULTS: There were no clinical complications other than two superficial wound infections. The sealing of the cystic duct and artery were both macroscopically and microscopically 100% sufficient. The maximum extension of the coagulative process in the sealed ducts was 0.25 mm on each side of the sealed area. CONCLUSIONS: The Ligasure system seems promising for securing the cystic duct and artery during cholecystectomy. Future studies should evaluate safety with this technique on a larger scale.
Tumor cell differentiation by butyrate and environmental stress.
The present study shows that stress signaling plays a role in differentiation of K562, PANC1, HT29 and HL60 tumor cells: (1) Butyrate induced differentiation in K562, PANC1, and HT29 cells can be inhibited by SB203580, a specific inhibitor of p38 stress activated protein kinase. (2) Heat shock and hyperosmolarity increase expression of differentiation markers in K562, HT29, HL60 and in K562, PANC1, and HT29 cells, respectively. (3) Conversely, environmental stress induced differentiation in K562, HT29, and PANC1 cells can be inhibited by SB203580 and quercetin, a compound with heat shock pathway inhibiting activity. (4) Butyrate and environmental stress enhance either additively or synergistically differentiation of K562, HT29, PANC1 or HL60 cells, respectively. Stress signaling pathways might be an interesting pharmacologic target for differentiation therapy of malignant disease.
[Development and challenges in abdominal surgery].
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Essential genes in proximal 3L heterochromatin of Drosophila melanogaster.
We have further characterized essential loci within the centric heterochromatin of the left arm of chromosome 3 (3L) of Drosophila melanogaster, using EMS, radiation and P element mutagenesis. We failed to find any new essential genes, a result that suggests a lower-than-average gene density in this region. Mutations affecting expression of the most proximal gene [lethal 1, l1 or l(3)80Fj] act as dominant suppressors of Polycomb (Pc), behavior which is consistent with a putative trithorax group (trx-G) gene. The third gene to the left of the centromere [lethal 3, l3 or l(3)80Fh] is likely to correspond to verthandi (vtd), a known trx-G gene that plays a role in the regulation of hedgehog (hh) expression and signalling. The intervening gene [lethal 2, l2 or l(3)80Fi] is required throughout development, and mutant alleles have interesting phenotypes; in various allelic combinations that survive, we observe fertility, bristle, wing, eye and cuticle defects.
[Treatment of common bile duct stones].
Open single-stage treatment of gallstones and common bile duct stones (CBDS) has previously been standard procedure. Endoscopic stone extraction after a sphincterotomy has become a well-established therapeutic modality during the last twenty years and is now the standard procedure. The available options for management of patients with CBDS are reviewed. Although there is no evidence concerning the best treatment of CBDS, it is concluded, that a two-stage procedure with endoscopic CBDS extraction followed by cholecystectomy has no advantages over a single stage open or laparoscopic procedure. In the future the treatment of CBDS will be differentiated depending on size of the stone, the occurrence of complications to CBDS and the general health of the patient.
[Transnasal gastroscopy].
The use of transnasal endoscopy has not been reported earlier in Denmark. This study describes the preliminary experiences with transnasal gastroscopy using the Olympus XGIF-N200 prototype. Patients scheduled for diagnostic gastroscopy were examined transnasally. The patients answered questions regarding anxiety and discomfort, and the endoscopist commented on the quality of the procedure. Of sixty patients included, 56 (93%) were examined transnasally. Two patients did not have nasal passage and were examined orally, and two patients were examined with standard gastroscope because of technical difficulties. Sixty-eight percent of the procedures were unsedated, 55% of the patients did not experience gag-reflexes. The procedure was described by most patients as "slightly uncomfortable". Twenty-five percent had uncomplicated epistaxis. Pulse rate and saturation levels were stable. Transnasal gastroscopy seems to be well tolerated by the patients, as both subjective and objective criteria were better than those for conventional gastroscopy.
Cloning and characterization of a new theta-class glutathione-S-transferase (GST) gene, gst-3, from Drosophila melanogaster.
We report here on the cloning and characterization of a new theta-class glutathione-S-transferase (GST) gene, gst-3, from Drosophila melanogaster. Its sequence is distinct from previously characterized Drosophila GST genes, and Southern blotting shows no other closely related genes in the genome. In-situ hybridization localizes the gene to chromosome 2 (55D), near gst-2 (53F), and clearly separate from the gst-D cluster at 87B. The gene is intronless and appears to possess conventional 5' TATA, Cap and 3' polyadenylation signals. A single transcript, approximately 1kb in size, appears to be expressed at high levels in all developmental stages examined. When this gene is overexpressed using various upstream GAL4 driver systems, no striking phenotypes are observed; however, we detect bristle morphology defects in some progeny. The gst-3 gene does not appear to be essential, based upon our observation that mutant flies homozygous for an EP element insertion 5' to the TATA box produce little or no detectable gst-3 mRNA; these flies are viable and fertile at 25 and 29 degrees C. Nevertheless, the gst-3 gene appears to be evolutionarily conserved in other Drosophila species, suggesting that it may be functionally important.
The effect of 7-oxo-DHEA acetate on memory in young and old C57BL/6 mice.
7-Oxo-dehydroepiandrosterone, which can be formed from dehydroepiandrosterone (DHEA) by several mammalian tissues, is more effective than its parent steroid as an inducer of thermogenic enzymes when administered to rats. Using the Morris water maze procedure, we tested DHEA and its 7-oxo-derivative for their ability to reverse the memory abolition induced by scopolamine in young C57BL/6 mice, and for their effect on memory in old mice. A single dose of 7-oxo-DHEA-acetate at 24 mg/kg b.w. completely reversed the impairment caused by 1 mg of scopolamine per kg b.w. (P < 0.001). DHEA (20 mg/kg) was also effective (P < 0.01). In old mice given the same single doses followed by feeding 0.05% of the respective steroid in the diet, memory of the water maze training was retained through a four week test period in mice receiving 7-oxo-DHEA-acetate (P < 0.05) but not in the control or DHEA-treated groups. When old mice were not tested until five weeks after being trained 7-oxo-DHEA exerted a slight, but statistically insignificant, improvement in memory retention. The possible effect of 7-oxo-DHEA in human memory problems deserves investigation.
Plasticity and stability of somatosensory maps in thalamus and cortex.
Work on elucidating the mechanisms of plasticity in somatosensory maps continues apace. Recent work has focused on both the nature of the thalamocortical interactions that determine plasticity, and on the differences between plasticity induced by nerve block or damage versus that induced by experience. Recordings from awake behaving animals have thrown light on the thalamocortical circuit mechanisms that underlie map plasticity; meanwhile, intracellular recordings from cortical slices have thrown light on the precise synaptic mechanisms underlying plasticity.
Essential genes in autosomal heterochromatin of Drosophila melanogaster.
We are taking two approaches to understanding the structure, function and regulation of essential genes within Drosophila heterochromatin. In the first, we have undertaken a genetic and molecular characterization of essential genes within proximal 3L heterochromatin. The expression of such 'resident' genes within a heterochromatic environment is paradoxical and poorly understood, given that the same environment can inactivate euchromatic sequences (position effect variegation, or PEV). A second approach involves the study of the local chromosomal environment of heterochromatic (het) genes, as assayed both biochemically, and via the effects of genetic modifiers of PEV, the latter being putative components important for het gene expression. Our results to date suggest that the three most proximal genes in 3L heterochromatin have key roles in development, and indicate strong effects of combinations of genetic modifiers of PEV on het gene expression.
[Air endotamponade in 52 vitrectomies due to proliferative diabetic retinopathy--retrospective comparison with 40 vitrectomies without endotamponade].
BACKGROUND: In patients with proliferative diabetic retinopathy rebleeding after pars plana vitrectomy is one of the most common complications. We tried to reduce the rate of that complication by using an air endotamponade. PATIENTS AND METHODS: The following study is a retrospective comparison of 2 patient groups both after pars plana vitrectomy due to proliferative diabetic retinopathy. Group 1 was managed with air as endotamponade (n = 52, mean age 61.2 years), group 2 without any endotamponade (n = 40, mean age 59.4 years). Classification of the proliferative diabetic retinopathy as described by Kroll et al. [5] in both groups: 23 and 29 patients with stage A resp., 24 and 10 patients with stage B resp., 5 and 1 patient with stage C respectively. RESULTS: 77% of group 1 patients had an increase os vision by mean of 4.8 vision steps, in 70% of the group 2 patients vision increased by mean of 7.2 vision steps. Complications in both groups as follows: Rebleeding within 14 days 15% vs. 33%, development of secondary glaucoma in 9.6% and 17.5% resp., revitrectomy within 14 days were necessary in 3.8% resp. 2.5% of the patients, later revitrectomy in 13.5% vs. 42.5% of all patients. SUMMARY: Air endotamponade turned out to be appropriate to reduce the rate of postoperative vitreous rebleeding after pars plana vitrectomy due to proliferative diabetic retinopathy. We found no increase of secondary glaucoma or cataract.
Vagal withdrawal during endoscopic retrograde cholangiopancreatography.
BACKGROUND: Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) are at risk of developing cardiorespiratory complications, but the mechanism is still unknown. Treatment with metoprolol 2 h before the endoscopy has been shown to decrease the incidence of myocardial ischaemia during ERCP. The present study evaluated whether the endoscopic stress would decrease vagal tone and whether metoprolol given before the procedure could prevent this defence-like reaction. METHODS: Thirty-eight patients were randomized to receive either placebo or 100 mg metoprolol 2 h before ERCP. During ERCP the patients were monitored with a Holter tape recorder. Holter tapes from 31 patients (16 receiving metoprolol) were available to analyse the ratio of the standard deviations of the RR intervals (SDRR) to the mean RR intervals (measure of vagal tone) during ERCP. RESULTS: A decreased vagal tone during the ERCP was found, but we observed no difference between the metoprolol and the placebo group. For both groups the lowest vagal tone occurred at maximum heart rate during endoscopy. The SDRR/meanRR ratio returned towards base line for the subsequent 60 min after endoscopy. CONCLUSIONS: The existence of a defence-like reaction ('vagal withdrawal') during ERCP has been shown. Metoprolol given 2 h before the procedure did not affect the occurrence of this phenomenon. The interaction of other periendoscopic factors is still unclear and should be studied further.
Transnasal gastroscopy.
INTRODUCTION: The use of transnasal gastroscopy (TNG) has not previously been described in a Danish hospital. The method seems to be better tolerated compared with conventional oral gastroscopy. METHODOLOGY: Patients scheduled for diagnostic gastroscopy were included, and examined with a thin endoscope transnasally (Olympus XGIF-N200 prototype, diameter 6 mm). RESULTS: Sixty patients were included, and transnasal gastroscopy was possible in 56 patients (93%). Two patients were examined transorally, as there were no passage through the nose. One patient had fluid retention in the stomach, and in another patient the endoscope looped continuously in the esophagus, preventing introduction into the stomach. The quality in 48 examinations (80%) was satisfactory. Unsedated examination was possible with 38 patients (68%), and 55% of patients did not have gag-reflexes or nausea. The unpleasantness of TNG was rated on a scale from 1 to 4, and the median score was 2 (slightly unpleasant). TNG would be the method of choice in 88% of patients, if they should undergo another gastroscopy in the future. Fifteen patients had uncomplicated epistaxis as the only complication. Pulse rate and oxygen saturation values were stable during the TNG examinations. CONCLUSION: TNG with a thin endoscope seems to be well tolerated by the patients, this is supported by the subjective experience of the patients, and also by the stable values of oxygen saturation and heart rate during the examinations.