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Biomedical subjects

M Gregor

Publications and source records attributed to M Gregor.

At least 55 records · Page 3Linked to original sources

[Effects of biphasic spiral CT, conventional and iron oxide enhanced MRI on therapy and therapy costs in patients with focal liver lesions].

PURPOSE: Evaluation of the diagnostic efficacy and cost-benefit of contrast enhanced CT (CT) and MRI pre- and post-SPIO-particles in focal hepatic disease with consideration of therapeutic outcome. METHODS: In 52 patients with the suspicion of primary or secondary hepatic malignancy, biphasic spiral CT and breath-hold gradient-echo T1- and fast spin-echo T2-weighted MRI pre- and post-iron oxide administration (1.5 T, body-phased-array coil) were compared. The number of hepatic lesions and the related diagnoses resulting from each imaging modality were recorded and statistically correlated to the final diagnoses established by biopsy/OP (34/52), long term follow-up of 12 months (18/52), and a consensus reading of all imaging modalities considering all clinical imaging information. The most likely induced therapy resulting from each imaging test was correlated to the final therapy. Based on data from the hospitals accountants, the therapy-related costs were estimated without hospitalization costs. RESULTS: In 34/52 (65.4%) of the cases the correct diagnosis was primarily stated by CT (sensitivity [se.] 85.2%, specificity [sp.] 44.0%). In additional 10/52 of the cases unenhanced MRI (se. 91.4%, sp. 75.0%) enabled correct diagnoses, and in another 6 cases the diagnosis was established only by SPIO-MRI (se. 100%, sp. 86.7%). Considering the possible therapeutic recommendation arising from each modality, CT would have induced needles therapy costs of 191,042 DM, unenhanced MRI of 171,035 DM, and SPIO-MRI of 7,311 DM. In comparison to the real therapy costs of 221,873 DM, this would have corresponded to an unnecessary increase of therapy costs of 86.1%, 77.1%, and 3.3%, respectively. In two cases (1 hemangioma, 1 regenerative nodule) all modalities failed, causing unnecessary surgery in one patient. DISCUSSION: In this problem-oriented scenario unenhanced and SPIO-enhanced MRI proved to be superior to CT regarding diagnostic efficacy. The cost-benefit resulted mainly due to preserving patients from unnecessary surgical procedures.

Adenoma, Liver Cell↗

C-reactive protein and fever in neutropenic patients.

The predictive value of daily C-reactive protein (CRP) monitoring to distinguish causes of fever in neutropenic patients was studied retrospectively. A total of 143 fever episodes during 113 consecutive hospitalizations were studied in 71 patients who had been referred for chemotherapy or haemopoietic stem cell transplantation (HSCT). There were, on average, 1.3 fever episodes per hospital stay, attributed to: infection (55, 27 invasive bacterial, 5 fungal, 3 viral and 20 probable infections); acute graft vs host disease (GvHD) (20); drugs (22); transfusions (7); and not attributable (39). 130 (91%) fever episodes were accompanied by a rise in CRP, 6 (4%) episodes were fatal. Maximal CRP levels (CRPmax) and maximal temperature (Tmax) were higher in invasive bacterial infections than in aGvHD and higher in aGvHD than in drug- or transfusion-related fever (p < 0.0001). Temperature and CRP rose in parallel. A total of 16 patients developed grade II-IV aGvHD by day 11 (9-21) (median, range) after allogeneic HSCT. Acute GvHD was preceded by fever for 3 d (1-7), and by CRP increase for 5 d (0-15) (p < 0.0001). CRP monitoring may be useful to distinguish between causes of fever. Very high CRP levels tend to be associated with invasive bacterial infections. CRP is not an early warning sign. An increase in CRP and fever may precede other clinical manifestations of aGvHD.

Adolescent↗

Expression and function of Na+HCO3- cotransporters in the gastrointestinal tract.

The stomach, duodenum, colon, and pancreas secrete HCO3- ions into the lumen. Although the importance of HCO3- secretion for the maintenance of mucosal integrity, a normal digestion, and the reabsorption of Cl- has been well established, the molecular nature of the apical and basolateral HCO3- transporting proteins has remained largely unknown. Functional studies have suggested that a Na+HCO3- cotransport system, similar but not identical to the well-characterized Na+HCO3- cotransporter in the basolateral membrane of the kidney proximal tubule, is present in duodenal and colonic enterocytes, pancreatic ducts cells, and gastric cells and involved in HCO3- uptake from the interstitium. This report describes our work towards understanding the molecular nature, cellular origin, and functional relevance of the Na+HCO3- cotransporter(s) in the stomach and intestine and reviews work by others on the function and localization of Na+HCO3- cotransport processes in the gastrointestinal tract.

Animals↗

Three 5'-variant mRNAs of anion exchanger AE2 in stomach and intestine of mouse, rabbit, and rat.

AE2 is one of three known isoforms of the anion exchanger (AE) gene family. The use of alternative promoters, resulting in a tissue-specific transcript pattern, was reported for all AE genes. Three N-terminal variant AE2 subtypes are described: AE2a, AE2b, and AE2c. Although the basolaterally located parietal cell anion exchanger is known to be an AE2, the molecular identity of the basolateral and apical anion exchangers throughout the gut are still unknown. This article summarizes functional, immunohistochemical, and Western blot data demonstrating the basolateral localization of the gastric and intestinal AE2 in rabbit, mouse, and rat, and showing the AE2 subtype mRNA expression pattern in the stomach and along the intestine of rabbit and mouse: AE2a is expressed in all studied tissues, but most strongly in the colon; AE2b is expressed mainly in the stomach; and AE2c is detected nearly exclusively in the stomach. Further investigation is necessary to characterize the apical anion transport protein involved in NaCl absorption and HCO3- secretion in the gut.

5' Untranslated Regions↗

MR imaging and (1)H spectroscopy of brain metabolites in hepatic encephalopathy: time-course of renormalization after liver transplantation.

PURPOSE: To evaluate changes in hydrogen 1 magnetic resonance (MR) spectroscopic findings in overt or subclinical hepatic encephalopathy (HE) after liver transplantation and to compare these changes with clinical outcomes and basal ganglia high signal intensity (BGH). MATERIALS AND METHODS: Twenty-two patients scheduled for liver transplantation and 17 healthy control subjects were examined with (1)H MR spectroscopy and standard nonenhanced MR imaging. Eight patients underwent complete MR imaging and (1)H spectroscopic examinations before liver transplantation and at 3-4-week, 12-28-week, and 10-12-month follow-up after liver transplantation. RESULTS: Before liver transplantation, typical (1)H spectroscopic changes-decreased myo-inositol (mI)/creatine (Cr) and choline (Cho)/Cr ratios and an elevated glutamine and glutamate (Glx)/Cr ratio-were found in 21 patients. Eighteen patients had BGH at T1-weighted imaging. Three to 7 months after liver transplantation, the mI/Cr and Glx/Cr ratios were within the normal range in five of eight and eight of eight patients, respectively, without any residual signs of subclinical or overt HE; however, at MR imaging, seven patients still had BGH. CONCLUSION: After successful liver transplantation, renormalization of HE-specific brain metabolite changes is detected at (1)H spectroscopy and precedes the disappearance of BGH. The neuropsychologic signs of subclinical or overt HE follow the changes seen at (1)H spectroscopy rather than those seen at MR imaging.

Adult↗

Agonist-induced cytoplasmic volume changes in cultured rabbit parietal cells.

Concomitant Na(+)/H(+) and Cl(-)/HCO(3)(-) exchange activation occurs during stimulation of acid secretion in cultured rabbit parietal cells, possibly related to a necessity for volume regulation during the secretory process. We investigated whether cytoplasmic volume changes occur during secretagogue stimulation of cultured rabbit parietal cells. Cells were loaded with the fluorescent dye calcein, and the calcein concentration within a defined cytoplasmic volume was recorded by confocal microscopy. Forskolin at 10(-5) M, carbachol at 10(-4) M, and hyperosmolarity (400 mosmol) resulted in a rapid increase in the cytoplasmic dye concentration by 21 +/- 6, 9 +/- 4, and 23 +/- 5%, respectively, indicative of cell shrinkage, followed by recovery to baseline within several minutes, indicative of regulatory volume increase (RVI). Depolarization by 5 mM barium resulted in a decrease of the cytoplasmic dye concentration by 10 +/- 2%, indicative of cell swelling, with recovery within 15 min, and completely prevented forskolin- or carbachol-induced cytoplasmic shrinkage. Na(+)/H(+) exchange inhibitors slightly reduced the initial cell shrinkage and significantly slowed the RVI, whereas 100 microM bumetanide had no significant effect on either parameter. We conclude that acid secretagoguges induce a rapid loss of parietal cell cytoplasmic volume, followed by RVI, which is predominantly mediated by Na(+)/H(+) and Cl(-)/HCO(3)(-) exchange.

Amiloride↗

[Initial manifestation of primary intestinal lymphangiectasis as acute abdomen].

HISTORY: A 32-year-old man had ten years previously undergone several laparotomies for recurrent ileus of the small intestine. They revealed severe intestinal oedema and histology showed hyperplasia of the lymphatic system but the aetiology was unclear. After a 10-year interval free of symptoms he presented with marked hypoproteinaemic oedema and exudative enteropathy the cause of which was to be clarified by exploratory laparotomy with excision of lymph nodes and a small section of small intestine. INVESTIGATIONS: Histology revealed intestinal lymphangiectasis with partly hyperplastic lymphoid tissue. Lymphangiography demonstrated several lymph nodes in the region of the aortic bifurcation and renal vessels with a central filling defect. It is thought likely that obstruction to lymphatic flow in this region resulted in oedema of the intestinal wall which caused the recurrent episodes of ileus. DIAGNOSIS: Retrospectively it is assumed that primary intestinal lymphangiectasis was responsible for the initial manifestation of an acute abdomen. For treatment of hypoproteiaemia with human albuminea prot system was implanted. The course was complicated by recurrent inflammation and thrombosis of the port catheter. Because of immune deficiency risk of carcinoma is high in primary intestinal lymphangiectasis. CONCLUSION: Primary intestinal lymphangiectasis, even though a rare condition, should be considered in the differential diagnosis of otherwise unclear acute abdomen.

Abdomen, Acute↗

[Multiple endocrine neoplasia Type I. Diagnosis and therapy in a case with classical family history].

BACKGROUND: A classical family history, representative of the multiple endocrine neoplasia type I (MEN I) syndrome, is reported to illustrate the clinical manifestations, diagnostic procedures and therapeutic modalities of the various endocrine disorders of this syndrome. DIAGNOSIS: Today genetic analysis clearly identifies gene carriers. In these patients screening of all involved endocrine organs (parathyroid, pituitary, pancreas) at regular time intervals is necessary because also at higher ages additional endocrine manifestations may develop. Due to consequent screening the age at time of diagnosis was reduced by 10 to 20 years. As a consequence the rate of malignancy of pancreatic endocrine tumors which is the limiting factor with regard to long-term prognosis was reduced to about one third. At present it is not known whether this procedure can also increase the survival rate of MEN I patients as could be demonstrated in the MEN II syndrome.

Genetic Testing↗

Influence of p53 status on prognosis in preoperatively irradiated rectal carcinoma.

BACKGROUND: Even when they are analogous in microscopic and macroscopic appearance, tumors vary in their response rates to radiotherapy. Cell culture and xenograft experiments with colorectal cell lines have demonstrated that wild-type p53 increases radiosensitivity. Hence, the authors investigated, in a well-defined population of patients treated at the same institution, whether p53 status was a prognostic factor in preoperatively irradiated rectal carcinoma patients. METHODS: The p53 status of rectal adenocarcinomas was examined immunohistochemically (with monoclonal antibody DO-1) in preirradiated biopsy samples (n = 100) and corresponding postirradiated resected specimens (n = 97). The mean follow-up was 73.2 months (median, 71.3 months; range, 4.3-157 months). Statistical analysis was performed using the SPSS program (SPSS, Chicago, IL). RESULTS: p53 protein expression was detected in 55 of 100 biopsy samples (> or = 5% nuclear staining). There was essentially no difference in p53 expression between biopsy samples and corresponding resected specimens (54 of 97 vs. 55 of 97). In univariate analysis, p53 immunoreactivity of biopsy samples did not correlate with age, gender, tumor location, TNM stage, pT category, pN category, or histologic grade. Unlike clinicopathologic variables, p53 expression did not have a statistically significant association with local recurrence free, disease free, or overall survival in either univariate (P = 0.91, 0.18, and 0.17, respectively) or multivariate analysis. CONCLUSIONS: In contrast to cell line studies, this immunohistochemical study demonstrates that p53 status is not useful as a prognostic marker in preoperatively irradiated rectal carcinoma.

Adenocarcinoma↗

Microenvironment of the high affinity ATP-binding site of Na+/K+-ATPase is slightly acidic.

Fluorescein-5'-isothiocyanate (FITC) was used to study the high-affinity ATP-binding site of Na+/K+-ATPase. The molar ratio of specifically bound FITC per alpha-subunit of Na+/K+-ATPase was found to be 0.5 as followed from pretreatment experiments with another specific E1ATP-inhibitor Cr(H2O)4AdoPP[CH2]P. This indicated an existence of one high affinity ATP-binding site (E1ATP-binding site) in the native (alphabeta)2-diprotomer of Na+/K+-ATPase. Fluorescence dual-excitation ratio of specifically bound FITC revealed that at external pH 7.5, the pH value inside the E1ATP-binding site is 6.95 +/- 0.18. In addition, FITC fluorescence quenching by anti-fluorescein and by iodide choline indicated the limited access of water into the small pocket of the E1ATP-binding site.

Adenosine Triphosphate↗

T2-weighted breathold imaging of the liver: a quantitative and qualitative comparison of fast spin echo and half Fourier single shot fast spin echo imaging.

The imaging characteristics of two EPI-hybrid breath-hold sequences, T2-weighted fast spin-echo [FSE, effective echo time (TEeff) 138 ms] and half Fourier single shot turbo spin-echo (HASTE, TEeff 60 ms), were compared in hepatic imaging. A total of 111 patients with suspected hepatic disease were studied at 1.5 Tesla using a body phase-array coil. The signal-to-noise (S/N) and contrast-to-noise (C/N) ratios for organs and lesions were calculated and quantitatively compared. Organ delineation, visualization of anatomical structures and pathological lesions, artifacts, and total image quality were qualitatively assessed and statistically compared. The final diagnoses were metastases from colorectal, breast, and pancreatic cancer in 23/111, hepatocellular carcinoma in 15/111, cysts in 19/111, hemangiomas in 9/111, several other lesions in 7/111, and no lesions in 38/111 of the cases. A total of 139 lesion in 73% of the patients were seen while 85% of the lesions were at least 1.5 cm in size. Regarding S/Ns HASTE was significantly (P < 0.03) superior to FSE with only minor (P > 0.05) differences in C/Ns between the two sequences for anatomical and pathological structures. HASTE demonstrated in almost all (97.3%) of the cases no artifacts, while on fast SE imaging moderate to minor artifacts were present in 23.5-51.7% of the cases. The overall image quality and diagnostic confidence was rated significantly higher (good 43.2%, excellent 53.2%) for HASTE than for fast SE imaging (good 44.8%, excellent 17.6%). Providing comparable C/Ns for anatomical and pathological structures, breatheld HASTE imaging proved to be superior to fast SE in T2-weighted imaging of the upper abdomen regarding general image quality, and, with adequate technical prerequisites, may be a suitable substitute of fast T2-imaging techniques.

Evaluation Studies as Topic↗

[Comparison of dual-phase helical CT with native and ferum oxide-enhanced magnetic resonance imaging in detection and characterization of focal liver lesions].

PURPOSE: Evaluation of the diagnostic efficacy of contrast-enhanced, dual-phase spiral CT and MRI before and after administration of SPIO particles in focal hepatic disease with previously uncertain diagnosis. MATERIAL AND METHODS: In 46 patients in whom primary or secondary hepatic malignancy was suspected, dual-phase spiral CECT and breath-held T1-weighted gradient-echo and T2-weighted fast spin-echo MRI (1.5 T, body-phased-array coil) before and after SPIO administration were compared. The indications for the subsequent MRI studies were based on ambiguous findings on CECT. The number of hepatic lesions, the overall lesion detection and characterization was evaluated by consensus and compared to the gold standard (histological proof in 30/46 of the cases, long-term follow-up in 16/46 of the cases). RESULTS: In 34 of 46 cases the correct diagnoses were established by CECT (sensitivity 96%, specificity 48%) revealing significantly less lesions than MRI. Unenhanced MRI had sensitivity of 93% and specificity of 71%, whereas SPIO-enhanced MRI had sensitivity of 97% and specificity of 88%. The differences between the modalities were even more pronounced in the detection of lesions smaller than 10 mm with SPIO-MRI as the most sensitive method. CONCLUSIONS: In this problem-oriented scenario, SPIO-enhanced MRI was superior to spiral CT and unenhanced MRI regarding the diagnostic efficacy in the pre-operative work-up of focal liver lesions. SPIO-enhanced MRI can be recommended as a problem-solving tool for the clinical routine.

Adult↗

Na+/HCO3- cotransport and expression of NBC1 and NBC2 in rabbit gastric parietal and mucous cells.

BACKGROUND & AIMS: The gastric epithelium protects itself against luminal acid by secreting HCO3--rich fluid into the mucous layer and by HCO3--dependent intracellular pH regulation, but the basolateral HCO3- uptake mechanisms are incompletely characterized. This study examined the expression and functional significance of the Na+/HCO3- cotransporters NBC1 and NBC2 in rabbit gastric epithelial cells. METHODS: Rabbit NBC1 and NBC2 complementary DNA fragments were cloned and sequenced, and cellular expression levels were assessed by semiquantitative polymerase chain reaction. Na+/HCO3- cotransport activity was measured fluorometrically in cultured rabbit parietal and mucous cells. RESULTS: NBC1 expression was 4.5-fold lower in the stomach than kidney cortex and 5.5-fold higher in mucous than parietal cells. NBC2 expression in the stomach was much lower than in the eye, approximately 4-fold lower than NBC1 expression in the stomach, and 2.5-fold higher in mucous than parietal cells. The Na+- and HCO3--dependent, dimethylamiloride-insensitive (which at 500 micromol/L completely inhibits all Na+/H+ exchanger isoforms) base influx rates were 4.6 +/- 0.02 and 16.2 +/- 0.04 mmol/L/min in acidified parietal and mucous cells, respectively, and were not significantly different in the absence of Cl-. CONCLUSIONS: This study shows that NBC1 and NBC2 are expressed in rabbit stomach, with high levels in mucous cells where Na+/HCO3- cotransport is the major base-importing mechanism in the presence of CO2/HCO3-.

Animals↗

Graft-versus-myeloma after withdrawal of immunosuppression following allogeneic peripheral stem cell transplantation.

There is growing evidence for a graft-versus-myeloma effect following allogeneic stem cell transplantation. We add to this evidence by reporting complete remission achieved by withdrawal of immunosuppression in a patient with multiple myeloma progressing after HLA-identical sibling peripheral stem cell transplantation. De novo chronic graft-versus-host disease coincided with the anti-myeloma effect and responded to treatment. The patient remains in complete remission 3 years after transplant.

Adult↗

Repeated peripheral stem cell mobilization in healthy donors: time-dependent changes in mobilization efficiency.

Mobilization of peripheral blood stem cells was analysed in 10 consecutive healthy donors undergoing repeated stem cell mobilization for allogeneic transplantation. Donors received recombinant G-CSF at a dose of 10 microg/kg/d for both mobilizations. Collection of stem cells was started on day 5 of G-CSF administration. To compare the efficiency of first and second mobilization, we determined the leucocyte and CD34+ cell counts in peripheral blood, and the yield of nucleated cells and CD34+ cell counts in the apheresis product. CD34+ cell numbers in peripheral blood were (median) 81.2 x 10(6)/l during the first and 50.4 x 10(6)/l during the second mobilization (P = 0.007). Likewise, CD34+ cells in the apheresis product decreased from 319.8 x 10(6) to 275.7 x 10(6) (P = 0.02). Decrease in CD34+ cell counts in peripheral blood and in the apheresis product was associated with the time interval between first and second mobilization. In a regression analysis there was a correlation between the ratios of CD34+ cell counts of first and second mobilization and the inverse of time interval between procedures (r2 = 0.51 peripheral blood; r2 = 0.74 apheresis product). Thus, stem cell yield is reduced when healthy donors receive repeated mobilization within a short time. Nevertheless, an adequate number of stem cells may repeatedly be mobilized within 2 months.

Antigens, CD34↗

Sendai virus infection induces apoptosis through activation of caspase-8 (FLICE) and caspase-3 (CPP32).

Sendai virus (SV) infection and replication lead to a strong cytopathic effect with subsequent death of host cells. We now show that SV infection triggers an apoptotic program in target cells. Incubation of infected cells with the peptide inhibitor z-VAD-fmk abrogated SV-induced apoptosis, indicating that proteases of the caspase family were involved. Moreover, proteolytic activation of two distinct caspases, CPP32/caspase-3 and, as shown for the first time in virus-infected cells, FLICE/caspase-8, could be detected. So far, activation of FLICE/caspase-8 has been described in apoptosis triggered by death receptors, including CD95 and tumor necrosis factor (TNF)-R1. In contrast, we could show that SV-induced apoptosis did not require TNF or CD95 ligand. We further found that apoptosis of infected cells did not influence the maturation and budding of SV progeny. In conclusion, SV-induced cell injury is mediated by CD95- and TNF-R1-independent activation of caspases, leading to the death of host cells without impairment of the viral life cycle.

Animals↗