Biomedical subjects
Publications and source records attributed to F Meyer.
Iatrogenic pseudomeningocele formation after lumbar or cervical spine surgery is a well-described complication. Two unusual cases of transdural nerve root herniation with subsequent entrapment in the intervertebral space after lumbar disc surgery are presented. The reasons for this rare complication and its treatment are discussed.
A new approach for access to the right atrium via the superficial-temporal vein is proposed. We prefer this route whenever anterior neck veins cannot be used to place the catheter into the right atrium, e.g., in patients with tracheostomy. The results seem to be as good as those obtained with conventional techniques.
The new CCK-B/gastrin receptor antagonist PD 136450 is of potential value in treating neurologic and psychiatric disorders. We investigated possible side effects on the rat pancreas using acute and chronic administration schedules. In chronic experiments, four groups of rats were given either PD 136450, the proton pump inhibitor BY 308 (in order to induce hypergastrinemia), a combination of both, or control solutions over 14 d. Pancreatic growth, DNA, and protein content were significantly increased in rats given PD 136450 irrespective of circulating gastrin levels. Furthermore, an anticoordinate shift in pancreatic enzyme content in favor of trypsin and chymotrypsin at the expense of amylase and lipase was observed. Plasma CCK levels remained unchanged in this group making a role of circulating hormone unlikely. In order to investigate a possible direct agonist effect of the CCK-B/gastrin receptor antagonist, we studied amylase release from isolated rat pancreatic acini in response to PD 136450 and sulfated CCK8 alone and in combination with the specific CCK-A receptor antagonist MK 329. Increasing concentrations of PD 136450 caused a monophasic dose-response curve in contrast to the well-known biphasic amylase release in response to CCK8. Addition of increasing doses of PD 136450 to a concentration of CCK causing maximal stimulation of amylase release (0.1 nM) further enhanced amylase release from pancreatic acini. The specific CCK-A receptor antagonist MK 329 dose-dependently inhibited CCK8- and PD 136450-induced amylase release. In conclusion, the new CCK-B/gastrin receptor antagonist PD 136450 exhibited profound agonist actions on the rat pancreas mediated via CCK-A receptors.
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5-Fluorouracil (5-FU) has been claimed to have beneficial effects in human pancreatitis because of its ability to inhibit protein synthesis and secretion. However, the effect of 5-FU has not been studied in the pancreas of animals in more detail and the data in human pancreatitis are mostly derived from uncontrolled studies. Thus, we studied potential short-term effects of 5-FU on protein synthesis and secretion in isolated pancreatic acini from normal rats and from rats with sodium taurocholate-induced pancreatitis. Furthermore, we used the isolated perfused pancreas, damaged by taurocholate, to study whether arterial perfusion with 5-FU has any beneficial effects. When pancreatic acini were incubated with various concentrations of 5-FU, CCK-8-stimulated amylase secretion was not altered. Furthermore, 5-FU had no short-term effects on protein synthesis. Protein synthesis and secretion was already markedly depressed in isolated pancreatic acini derived from rats with sodium taurocholate-induced pancreatitis. 5-FU did not further decrease protein synthesis or secretion. Retrograde injection of sodium taurocholate in the main pancreatic duct of the isolated perfused pancreas resulted in a steep increase of amylase and lipase in the portal effluate. Arterial perfusion with 5-FU had no influence on enzyme release into the portal blood. We may conclude that our data, derived from experimental pancreatitis in rats, do not encourage investigation of the effect of 5-FU, an anticancer drug with possibly toxic side effects, in human pancreatitis.
This study examined changes in children's thirst and drink preferences during exercise-induced hypohydration and their spontaneous rehydration during a 30-min recovery. Twenty-four 9- to 13-year-old children (14 females, 10 males) participated in four intermittent 90-min cycling sessions in the heat (35 degrees C, 20% relative humidity); the sessions differed in the drinks the children were sampling (apple, orange, water, and grape). Thirst and drink preferences were assessed (analog and category scales) while children dehydrated up to about 0.76% of their initial body weight. During 90 min dehydration, there was an increase in thirst intensity for all drinks. The grape was the preferable drink throughout the dehydration phase, but its desirability did not increase as much as the desirability of the orange, apple, and water drinks. During the 30-min recovery, most subjects rehydrated spontaneously, exceeding baseline levels by 0.76 +/- 0.15% (M +/- SEM) for grape, 0.40 +/- 0.15 for apple, 0.71 +/- 0.18 for orange, and 0.48 +/- 0.16 for water. Although full rehydration was achieved with all drinks, the magnitude of rehydration was statistically greater with grape and orange than water and apple (p < .05). It was concluded that mild hypohydration during exercise increased children's thirst and drink desirability. In general, spontaneous overshoot of fluid consumption occurred during recovery.
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In this study we investigated 213 forearm-fistulas, 233 elbow-fistulas, 21 bridge-fistulas and 3 axillo-axillary vascular accesses. 129 revisions were necessary to preserve the vascular access. The patency rates of the 170 primary forearm fistulas and the 140 primary elbow fistulas were 45 resp. 54%. We preferred the end-to-end-anastomosis for the forearm position and for the elbow the side-to-end-anastomosis. There were no differences between the type of anastomosis, localization and the second constructions as regards the patency rates. The results of the-end-to-end-fistulas were much better in male than female patients. Besides we had better results after thrombectomy in the elbow position compared to the forearm position. We found that a vein diameter less than 2 mm gave worse results. The most frequent complication of the fistulas was the thrombosis. Autologous and alloplastic transplants (grafts) were only taken if it wasn't possible to create an arteriovenous fistula by the orthotopic vessels.
Differential diagnosis between spondylotic cervical myelopathy and multiple sclerosis or other neurologic conditions may occasionally be difficult. Problems establishing the correct diagnosis are mentioned, topical literature is discussed and four criteria to establish the diagnosis of compression myelopathy are presented. We conclude that demyelinating diseases should be excluded prior to surgical management of cervical compression myelopathy because surgical intervention can result in marked worsening of symptoms.
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A population-based case-control study was conducted from 1985 to 1989 in western Washington State to assess the relation between nutrients and the incidence of colon cancer in men and women aged 30-62. A food frequency questionnaire was used to document the usual diet 7 years before diagnosis for 424 cases and at a similar time for 414 controls. Alcohol consumption was strongly related to the risk of colon cancer in both men and women, with age-adjusted odds ratios (ORs) of colon cancer = 1.0, 1.9, 1.7, and 2.6 for 0, < 10, 10-29, and > or = 30 g/day intake for men and adjusted odds ratios = 1.0, 1.3, 1.8, and 2.5 for the same categories for women. The trend odds ratio associated with a one-category increment in the four-level alcohol consumption variable was 1.3 (95% confidence interval (CI) 1.0-1.5) in men and 1.4 (95% CI 1.0-1.7) in women. For both sexes, higher dietary fiber intakes were associated with lower relative risks for colon cancer, with age-, energy-, and alcohol-adjusted odds ratios = 1.0, 0.9, 0.8, and 0.6 across quartiles of consumption for men (trend OR for a one-quartile increment = 0.8, 95% CI 0.7-1.1) and adjusted odds ratios = 1.0, 0.9, 0.5, and 0.5 for women (trend OR = 0.8, 95% CI 0.6-1.0). In men, this was mostly attributable to intake of cereal fiber (trend OR = 0.8, 95% CI 0.6-1.0) while, in women, this association mostly reflected the effect of fruit fiber (trend OR = 0.8, 95% CI 0.6-0.9) and vegetable fiber (trend OR = 0.8, 95% CI 0.7-1.0). Calcium was associated with a decreased risk of colon cancer among women only (adjusted OR across quartiles = 1.0, 0.5, 0.6, 0.3; trend OR = 0.7, 95% CI 0.6-1.0). There was no indication of an association between colon cancer and fat or protein consumption or dietary vitamins.
Highly metastatic alpha/beta-interferon (IFN-alpha/beta)-resistant Friend leukemia cells (FLC) were transfected with a retroviral vector (pLTneoL-5) containing the mouse IFN-alpha 1 gene. Transfected clones were isolated and tested for their capacity to secrete IFN-alpha 1 and their tumorigenicity when injected s.c. into immunocompetent syngeneic DBA/2 mice. Almost all FLC clones producing IFN in the range of 16-512 units/ml failed to grow when injected s.c. or i.p. into normal mice, whereas control FLC (transfected with a vector without the IFN gene) exhibited the highly malignant phenotype of the original FLC. High levels of IFN were detected in peritoneal fluid, tumor extracts, and sera of mice given injections of IFN-producing cells. Injection of mice with antibodies to IFN-alpha/beta resulted in the development of tumor ascites in mice transplanted i.p. with IFN-producing FLC. In contrast to the tumor rejection observed in immunocompetent mice, IFN-producing FLC were highly tumorigenic when transplanted into immunosuppressed nude mice. Mice given injections of IFN-producing FLC developed a long-lasting tumor-specific immune resistance to subsequent injection with highly metastatic FLC. Simultaneous s.c. injection of both metastatic FLC (approximately 10(3) 50% lethal doses) and IFN-producing cells resulted in potent inhibition of the tumor growth, with a survival rate of approximately 50% for injected mice. Contralateral injection (s.c.) of IFN-producing FLC into mice with established metastatic tumors produced a marked inhibition of tumor growth, with a survival rate of 10% for injected mice. These results indicate that: (a) the genetic modification of highly metastatic FLC by means of transfer of the IFN-alpha 1 gene results in potent tumor cell rejection, which is mediated by an IFN-induced host immune response; (b) injections of IFN-producing tumor cells are effective in inhibiting tumor growth in mice with established metastatic tumors. These data suggest that tumor cells transfected with the IFN-alpha gene might be used as an effective therapy for the treatment of certain human metastatic tumors, provided that suitable strategies are defined to prevent growth of the cytokine-producing cells.
Retroviral-mediated gene transfer of human beta-globin provides a model system for the development of somatic gene therapy for hemoglobinopathies. Previous work has shown that mice receiving a transplant of bone marrow cells infected with a retroviral vector containing the human beta-globin gene can express human beta-globin specifically in erythroid cells; however, the level of expression of the transduced globin gene was low (1% to 2% per gene copy as compared with that of the endogenous mouse beta-globin gene). We report here the construction of a recombinant retrovirus vector encoding a human beta-globin gene fused to the 4 major regulatory elements of the human beta-globin locus control region (LCR). The LCR cassette increases the level of expression of the globin gene in murine erythroleukemia cells by 10-fold. To study the level of expression in vivo, mouse bone marrow cells were infected with virus-producing cells and the transduced cells were injected into lethally irradiated recipients. In the majority of provirus-containing mice (up to 75%), expression of human beta-globin in peripheral blood was detected at least 3 to 6 months after transplantation. Twelve animals representative of the level of expression of the transduced gene in blood (0.04% to 3.2% of the endogenous mouse beta-globin RNA) were selected for further analysis. A range of 0.4% to 12% of circulating erythrocytes stained positive for human beta-globin protein. Based on these values, the level of expression of the transduced gene per cell was estimated to be 10% to 39% of the endogenous mouse beta-globin gene. These data demonstrate that fusion of the LCR to the beta-globin gene in a retroviral vector increases the level of beta-globin expression in murine erythroleukemia cells and suggest that high-level expression can be obtained in erythroid cells in vivo after transduction into hematopoietic stem cells.
A cDNA encoding a 63-kDa human IFN-alpha R (hIFN-alpha R) has recently been cloned. Mouse cells transfected with this cDNA failed to show any signal transmission for IFN-beta, suggesting the involvement of additional chains in the receptor complex. We have expressed in Escherichia coli and COS 7 cells a soluble recombinant protein (sIFN-alpha R) comprising the extracellular domain of the hIFN-alpha R fused at the carboxyl terminus to a sequence of five histidine residues. The sIFN-alpha R was affinity purified and used to generate mAb. One mAb, 64G12, which recognized the cellular receptor as well as the recombinant proteins was found to neutralize the biologic activity of IFN-alpha, -beta, and -omega and natural type I IFN, but not IFN-gamma. To our knowledge, this is the first report of a neutralizing mAb against the human IFN-alpha R. Interestingly, we found that the affinity of this antibody for the cellular receptor depended on the cell line used. These results provide strong evidence that the cloned hIFN-alpha R chain is required for binding and signal transmission of all subspecies of type I IFN and suggest a structural heterogeneity of the receptor at the cell surface.
Only few studies devoted to quantitative analysis of tissue architecture have been performed. The analysis of neighborhood relationships between cells, using graphs and mathematical morphology (MM), constitutes one approach. We propose to analyse quantitatively the architecture of a tissue with the tools of MM on graphs. The use of graphs seems best suited to take into account the neighborhood relationships between cells, independently from their mutual distances: two cells are considered as neighbors if no interfering cell is placed in a given sense between them. Such neighboring cells are linked by an arc in a graph. On such a graph, all tools of MM may be applied. We investigate two of them in the present work: (1) the distance transforms permits to analyse the repartition of a cellular population A relative to population B, (2) the size distribution permits to analyse the tendancy of a cell population to form clusters. We have applied this method using Gabriel's graph, derived from the Voronoï diagram, to determine the "zone of influence" of a cell. We have analysed the neighborhood relationships between cells in germinal centers (GC) from lymph nodes. Twelve hyperplastic GCs from follicular hyperplasia (FH) and 5 neoplastic GCs from small cleaved cell follicular lymphoma (++SCCFL) have been studied; 2 microns hematoxylin-eosin plastic embedded sections have been analysed. Cell nuclei have been identified manually by the observer by giving a numerical and image color code. Gabriel's graphs have been constructed with all centrofollicular cells. Subgraphs with only lymphoid cells, large cells or small cleaved cells have also been studied. The application of MM transformations on the graphs using software package Morphograph has allowed a quantitative description of cell distribution in the tissue. The distances of centrofollicular lymphoid cells from the periphery of the GCs (mantle zone), from nonlymphoid cells as macrophages located within the GCs and between large lymphoid cells and small lymphoid cells have been determined in FH and SCCFL. Using iterative closings and openings, we have detected aggregates of small and large cells and characterized their size and distribution in the GCs. The application of this method on lymph node biopsy has allowed a quantitative description and comparison of GCs in different pathological conditions.
Iatrogenic injuries of prevertebral structures during lumbar disc surgery area a rare albeit important complication, since they may be life-threatening. A short survey is given concerning the frequency and kind of prevertebral injuries as they are presented in the literature. Own experiences and a case of an AV-fistula following disc surgery are described. Finally, legal aspects of German law concerning the physician's duty to inform the patient of operative risks are discussed.