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T Keller

Publications and source records attributed to T Keller.

102 records · Page 6Linked to original sources

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Humans↗

Tissue factor is the only activator of coagulation in cultured human lung cancer cells.

It is a long-known principle that tumour cells tend to exploit the host's physiologic systems in order to get support in terms of, for example, nutrition, growth or metastasis. One of these physiologic systems is the blood coagulation cascade, which has been found activated in many tumour patients. The mechanisms of the activation of coagulation have been assessed in numerous animal and in vitro experiments, and the results appeared to point to several distinct activators. The present study used a large panel of different cultivated human lung cancer cell lines and experimental systems involving normal plasma, plasmas deficient of factors V, VII or X, purified coagulation factors II and X, recombinant tissue factor (TF), and specific inhibitory antibodies against factor VII and TF. The results provide strong evidence that there is no activator of coagulation besides TF in the wide array of lung cancer cells examined. However, this work reveals a striking variability of TF content among the cell lines. This might explain ambiguous results of clinical trials of anticoagulation as an adjunct to antineoplastic therapy in lung cancer. By sensitive diagnostic tools like the plasma thrombin-antithrombin complex levels it might be possible to select patients with activated coagulation, who might benefit from anticoagulation.

Antibodies↗

Vitamin K in combination with other biochemical markers to diagnose osteoporosis.

The significance of a multiparametric classification approach of vitamin K is analysed to differentiate premenopausal (CTRL), postmenopausal non-osteoporotic (nOSP) and osteoporotic (OSP) women. Data records of women between 28 and 74 years of age were used for evaluation. Bone mineral density was determined by quantitative computed tomography of the lumbar spine using the T-score to diagnose osteoporosis. Vitamin K and biochemical markers of bone formation and resorption--alkaline phosphatase (AP), bone alkaline phosphatase (bAP), osteocalcin (OC), undercarboxylated osteocalcin (ucOC), procollagen type I carboxyterminal propeptide (PICP), pyridinoline (PYD), deoxypyridinoline (DPD), N-terminal cross-linked telopeptide of type I collagen (NTx) and bone sialo protein (BSP)--were analysed in all women on days 1 and 42. Vitamin K was significantly lower in the OSP group versus nOSP and CTRL. The odds ratio results revealed the following: vitamin K, 16.7; PYD, 7.5; NTx, 6.0; DPD, 2.7; and ucOC, 2.7. Vitamin K represented a sensitivity rate of 64% and a specificity rate of 82%. In the receiver operating curve analysis, vitamin K reached the highest area under curve (AUC) score. The combination of vitamin K and AP, bAP and PYD resulted in increased AUC scores (>0.9). The parameter combination of vitamin K/PYD and vitamin K/bAP demonstrated a sensitivity rate of 75-88%, with a specificity rate of more than 82%. The data suggests that a combination of vitamin K with other biochemical bone indices might be a useful tool for assessing bone metabolism, especially in metabolic bone diseases such as osteoporosis.

Adult↗

Ethyl glucuronide: an unusual ethanol metabolite in humans. Synthesis, analytical data, and determination in serum and urine.

Ethyl glucuronide (ethyl beta-D-6-glucosiduronic acid), a minor ethanol metabolite in serum or urine, was determined by gas chromatography-mass spectrometry. Prior to this, ethyl glucuronide was synthesized by the reaction of acetobromo-glucosiduronic acid with ethanol. For the determination of ethyl glucuronide, serum samples were precipitated with acetone, and urine specimens were analyzed after evaporation to dryness. The residues were derivatized with acetic anhydride. Capillary gas chromatography was used to find a retention index value of 1920 for the triacetyl derivative. The mass spectrum of the acetylated ethyl glucuronide was recorded. The calibration is linear in the range investigated (0.1-150 mg/L), and the detection limit is 0.1 mg/L. In individual specimens containing between 0.1 and 4 g ethanol per liter serum, ethyl glucuronide could be detected at concentrations between 3 and 14 mg/L and in the corresponding urine specimens at concentrations between 3 and 130 mg/L.

Ethanol↗

Identification of benzene metabolites in dermal fibroblasts as nonphenolic: regulation of cell viability, apoptosis, lipid peroxidation and expression of matrix metalloproteinase 1 and elastin by benzene metabolites.

The skin is exposed to benzene and its derivatives, prevalent environmental chemicals. They may impair the structural integrity of the skin by increased expression of matrix metalloproteinase 1 (MMP-1; degrades structural collagen) and elastin, synthesized primarily by the dermal fibroblasts. We examined the metabolism of benzene in dermal fibroblasts and identified the benzene metabolites as toluene, benzaldehyde, aniline and benzoic acid. These metabolites were not toxic to the cells with regard to cell viability, apoptosis and lipid peroxidation, unlike the phenolic benzene metabolites (hydroquinone, t-butyl hydroquinone and phenol) or hydrogen peroxide. Toluene and phenol, which compose cigarette smoke, and benzaldehyde stimulated MMP-1 and/or elastin expression. In summary, the dermal fibroblasts metabolize benzene to nonphenolic metabolites that are less toxic to the cellular components than the phenolic benzene derivatives. Toluene, benzaldehyde and phenol can directly cause facial wrinkling and impaired structural integrity by upregulating MMP-1 and/or elastin.

Aniline Compounds↗

To reverse or not to reverse: an evaluation of reversal of mivacurium chloride in women undergoing outpatient gynecological procedures.

BACKGROUND: A double-blind, randomized study compared differences between patients administered edrophonium and those administered placebo after mivacurium infusion. Neuromuscular blockade was quantified using the ParaGraph 1800 nerve stimulator-monitor (Vital Signs, Totowa, NJ), which can deliver a train-of-four stimulus to the ulnar nerve and quantify the ratio of the fourth twitch to the first twitch. METHODS: With Investigational Review Board approval and informed consent, 30 healthy outpatient gynecological surgery patients ASA I or II, aged 21 to 37 years, were randomly assigned to treatment or placebo. In a double-blind manner, one group received edrophonium (1 mg/kg) and atropine (0.01 mg/kg) reversal (E/A) and the other group received placebo (P) to recover spontaneously from a mivacurium infusion. Anesthesia was induced and a rapid infusion of mivacurium chloride (0.2 mg/kg) was administered. An infusion of mivacurium chloride was then initiated at a rate of 6-7 microg/kg/min to maintain neuromuscular blockade. Group differences in recovery time (time between administration of the edrophonium or placebo and a 5-second head lift followed by tracheal extubation) were compared, as was time from tracheal extubation to discharge from the postanesthesia care unit (PACU). Nausea and vomiting were documented until the patient was discharged from the hospital; a 24-hour follow-up evaluation was completed by telephone. RESULTS: Each group contained 15 patients, and their demographics were similar. The mean recovery time for E/A was statistically shorter than for P (P, 9.7 +/- 4.8 minutes; E/A, 6.1 +/- 3.9 minutes; p = 0. 017). There were no statistically significant differences found in the incidence of nausea and vomiting (P, 4; E/A, 6) or in time to discharge from the PACU. CONCLUSION: Recovery from a mivacurium chloride infusion is shorter by 3.6 minutes (margin of error +/- 3.3 minutes) when reversal with edrophonium/atropine is used. There is no difference in time to discharge from PACU and no evidence of differences in nausea and vomiting.

Adult↗

Improved sensitivity of fuzzy logic based tumor marker profiles for diagnosis of pancreatic carcinoma versus benign pancreatic disease.

BACKGROUND: The definite diagnosis of pancreatic tumors of unknown origin remains a clinical challenge. Imaging techniques may fail to differentiate malignant tumors from inflammation, especially in chronic pancreatitis. In a considerable number of cases, the definitive diagnosis needs laparotomy. Single tumor markers as CA 19-9 or CEA are of limited value in these cases because of their limited sensitivity and specificity. This study was performed to find out, whether a classification method based on fuzzy logic analysis of tumor marker profiles is feasible in patients with pancreatic carcinoma and benign pancreatic disease. PATIENTS AND METHODS: Tumor markers and other clinical and laboratory parameters of 74 consecutive patients, either with histologically proved pancreatic carcinoma (n = 43) or presumed benign pancreatic disease (n = 31) assessed by ultrasound, endoscopic retrograde pancreatography, or computed tomography were analysed in order to detect their diagnostic value in the multi-dimensional approach of fuzzy logic analysis. RESULTS: Given a specificity of 95%, sensitivity was considerably increased by the fuzzy logic method (83%) compared with the best single tumor marker CA 19-9 (65%). CA 19-9, CYFRA 21-1 and CA 15-3 gave the most considerable contributions to the classification system, whereas CEA, CA 125, CA 72-4, AFP, liver enzymes, lipase, amylase, bilirubin, and ferritin were of no or little value. CONCLUSIONS: Tumor marker profiles analysed with the fuzzy logic method may have an improved sensitivity compared with single standard tumor markers. The diagnostic efficacy should be proved in patients with pancreatic tumors of unknown origin.

Adult↗