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Biomedical subjects

T Lutz

Publications and source records attributed to T Lutz.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacokinetics and tolerability of a combination of indinavir, lopinavir and ritonavir in multiply pretreated HIV-1 infected adults.

OBJECTIVES: The authors evaluated the pharmacokinetics and tolerability of indinavir/lopinavir/ritonavir in a protease inhibitor only combination. METHODS: Plasma drug levels of patients taking indinavir/lopinavir/ritonavir 800/400/100mg twice daily (n = 24, group 1) were compared to patients taking either lopinavir/ritonavir 400/100mg (n = 35, group2) or indinavir/ritonavir 800/100mg (n = 33, group3) twice daily plus nucleos(t)ide reverse transcriptase inhibitors (NRTI). Steady-state drug concentrations were measured by LC/MS/MS. Minimum and maximum concentrations (C subsetmin, C subsetmax), area under the concentration-time curve (AUC subset0-12h), total clearance (CL subsettot) and half-life (t1/2) were calculated. HIV viral load, CD4 cell count and adverse events causing early termination of therapy were correlated over a period of 48 weeks. RESULTS: Plasma levels of lopinavir/ritonavir were significantly enhanced when combined with indinavir compared to a regimen of lopinavir/ritonavir+NRTI: Mean lopinavir AUC subset(0-12h) 80,912 ng*h/mL vs. 60,548 ng*h/mL; C subsetmin 4,633 ng/mL vs. 3,258 ng/mL; C subsetmax 8,023 ng/mL vs. 6,710 ng/mL. Mean ritonavir AUC(0-12h) 6,907 ng*h/mL vs. 3,467 ng*h/mL; Cmin 220 ng/mL vs. 125 ng/mL; C subsetmax 1,059 ng/mL vs. 522 ng/mL. Indinavir levels were comparable for both indinavir containing regimen. A significantly smaller number of patients stopped indinavir/lopinavir/ritonavir therapy (group1: 16.7%) than indinavir/ritonavir + NRTI treatment (group3: 45.5%) due to adverse events. Virological failure was the main reason for early termination of treatment with indinavir/lopinavir/ ritonavir before week 48 (group1: 50%). CONCLUSIONS: indinavir/lopinavir/ritonavir 800/400/ 100mg twice daily represents a therapy option with an adequate safety but only short term efficacy for extensively pretreated patients.

Adult↗
PubMed2006

A randomized, open-label study to compare the effects of two different doses of recombinant human growth hormone on fat reduction and fasting metabolic parameters in HIV-1-infected patients with lipodystrophy.

BACKGROUND: Several studies have shown beneficial effects of recombinant human growth hormone (r-hGH) in reducing visceral adipose tissue (VAT) in HIV-1-infected patients with lipodystrophy. METHODS: Patients were randomized to r-hGH 4 mg daily (group A) or three times per week (group B) over 12 weeks, followed by a 2 mg daily maintenance dose for 12 weeks. Magnetic resonance imaging (MRI) scans were performed to assess body composition. RESULTS: A total of 26 subjects were included in the study. VAT was reduced overall by 35.1 cm(2) (29.5%) at week 12 and by 49 cm(2) (39.9%) at week 24, respectively, compared with baseline (P<0.001 for both comparisons). By week 12, VAT was reduced by 27 and 29% (A vs B; P=0.47) while facial fat was reduced by 3.3 and 2.6 cm(2) in groups A and B, respectively (P=0.96). Over 24 weeks, VAT was reduced by 42 and 38% (P=0.35) and facial fat by 3.2 and 2.4 cm(2) in groups A and B, respectively (P=0.91), compared with baseline. There was a greater increase in high-density lipoprotein (HDL) in group A than in group B (4.9 vs 2.4 mg/dL in week 12 and 7.1 vs -0.4 mg/dL in week 24; P=0.03). Fasting insulin levels increased, whereas glucose and insulin measured in oral glucose tolerance tests remained unchanged. Drug-related side effects were transient and reversible, but more common in group A (67%) than in group B (29%). CONCLUSIONS: This study confirms reports that r-hGH effectively reduces VAT, with a relatively small reduction of facial and limb fat.

Adipose Tissue↗
PubMed2005

[Efficiency of a herd health program in Swiss dairy herds].

A retrospective analysis of the reproductive parameters was conducted in 15 dairy farms using a herd health monitoring system between 1995 and 1998. Five of these farms have used this monitoring process for many years (group 1) while 10 of them only initiated the process in 1996 (group 2). It was the aim of this study to evaluate the economic gain of the farms in each group due to the herd health monitoring program throughout the three year study period, by using Value Based Management (VBM), a model from the economic sciences. The mean calving to conception interval decreased from 93.3 to 84.0 days and from 104.9 to 86.7 days throughout the study period in groups 1 (P>0.05) and 2 (P < 0.05), respectively. The mean percentage of cows with calving to conception intervals below 115 days varied between 68.2% and 82.0% in group 1, while there was an increase form 65.2% to 78.6% in group 2 (P<0.05). There were no apparent trends in the reproductive culling rate throughout the study period (P>0.05), and the majority fell below 10%. Likewise, the first service conception rate varied between 52.7% and 56.6% and between 41.2% and 50.0%, in group 1 and 2, respectively. The number of services per conception varied between 1.6 and 1.8 and between 1.8 and 1.9, in groups 1 and 2, respectively. The number of days between calving and first service varied between 62.7 and 64.8 days in group 1, while it decreased significantly from 69.2 to 59.2 in group 2 (P<0.05). The time between first service and conception decreased from 30.6 to 22.0 days, and from 35.7 to 28.0 days in groups 1 and 2, respectively (P<0.05). Although there was an apparent increase of the detection rate of oestrus from 57.8% to 68.2% throughout the study period in group 1, it was not significant (P > 0.05). In group 2, however, the oestrus detection rate increased significantly from 53.0% to 69.9% (P < 0.05). The percent of detected oestrus within 42 days post partum increased from 33.1% to 38.1%, and from 24.1% to 40.9% in groups 1 and 2, respectively (P < 0.05). By 1998, four out of five farms in group 1, and five out of the eight farms where information was avail- year study period of CHF 25.- to CHF 609.- per cow and year. The calving to conception interval and the reproductive culling rate were the two most important parameters to determine the reproductive performance of the herd and the economic benefit of the herd health monitoring program. These findings support the implementation of a herd health monitoring program.

Animal Welfare↗
PubMed2003

Phenylalanine can be detected in brain tissue of healthy subjects by 1H magnetic resonance spectroscopy.

Transport of phenylalanine (Phe) and the other large neutral amino acids across the blood-brain barrier plays a crucial role in the pathogenesis of phenylketonuria (PKU). Thus, investigation of Phe transport kinetics by means of proton magnetic resonance spectroscopy (1H MRS) became an important research area in the mid 1990s. As 1H MRS measurements of brain phenylalanine are restricted to tissue concentrations above 100-150 micromol/kg wet weight, this approach was possible only in PKU patients, and comparison with healthy controls was not achieved. Using standardized single-dose oral Phe loading in three healthy subjects, it was shown that Phe values increase steeply, peak at about 1 h post load, and decrease thereafter. In a single case study, repetitive Phe loading was then performed to achieve a plateau of high blood Phe concentrations for several hours. It was demonstrated that detection and monitoring of brain Phe concentrations is feasible by means of 1H MRS. This approach constitutes a prerequisite for describing carrier kinetics in health.

Adult↗
PubMed2001

The mitochondrial proteins Ssq1 and Jac1 are required for the assembly of iron sulfur clusters in mitochondria.

Mitochondria of the yeast Saccharomyces cerevisiae contain three different Hsp70 chaperones, Ssc1, Ecm10 and Ssq1. Ssc1 is an essential protein that mediates the import of nuclear-encoded proteins into the organelle and their subsequent folding. The nucleotide state of Ssc1 is thereby regulated by the nucleotide exchange factor Mge1. Here, we show that Mge1 interacts with Ssq1 in an ATP-dependent manner, suggesting that Mge1 also regulates Ssq1 function. In contrast to Ssc1, Ssq1 does not associate with the Tim44 subunit of the protein translocating complex, indicating a different function of both chaperones. Mutants in Ssq1 were reported to have low levels of iron sulfur (FeS) cluster-containing enzymes. Employing an assay that allowed us to monitor the conversion of the apoform of mitochondrial ferredoxin into its FeS-containing holoform, Ssq1 was demonstrated to be required for the FeS cluster assembly in mitochondria. The mitochondrial DnaJ homolog Jac1 is crucial for this process, whereas Mdj1 function is dispensable. Furthermore, the presence of frataxin is necessary for FeS cluster assembly into ferredoxin suggesting a role for frataxin at the level of the formation of holo-ferredoxin.

Adenosine Triphosphate↗
PubMed2001

Amylin potently activates AP neurons possibly via formation of the excitatory second messenger cGMP.

Amylin is secreted with insulin from the pancreas during and after food intake. One of the most potent actions of amylin in vivo is its anorectic effect, which is directly mediated by the area postrema (AP), a circumventricular organ lacking a functional blood-brain barrier. As we recently demonstrated, amylin also stimulates water intake most likely via its excitatory action on subfornical organ (SFO) neurons. Neurons investigated under equal conditions in an in vitro slice preparation of the rat AP were 15-fold more sensitive to amylin than SFO neurons. Amylin (10(-11)-10(-8) M) excited 48% of 94 AP neurons tested; the remaining cells were insensitive. The average threshold concentration of the excitatory response was 10(-10) M and, thus, close to physiological plasma concentrations. Coapplication of the amylin receptor antagonist AC-187 reduced amylin's excitatory effect. Amylin-mediated activation of AP neurons and antagonistic action of AC-187 were confirmed in vivo by c-fos studies. Peripherally applied amylin stimulated cGMP formation in AP and SFO neurons, as shown in immunohistochemical studies. This response was independent of nitric oxide (NO) formation in the AP, while coapplication of the NO synthase inhibitors N-monomethyl-L-arginine (100 mg/kg) and nitro-L-arginine methyl ester (50 mg/kg) blocked cGMP formation in the SFO. In contrast to the SFO, where NO-dependent cGMP formation seems to represent a general inhibitory transduction pathway, cGMP acts as an excitatory second messenger in the AP, since the membrane-permeable analog 8-bromo-cGMP stimulated 65% of all neurons tested (n = 17), including seven of nine amylin-sensitive neurons (77%). The results indicate that the anorectic effect of circulating amylin is based on its excitatory action on AP neurons, with cGMP acting as a second messenger.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Virological and immunological effects of treatment interruptions in HIV-1 infected patients with treatment failure.

OBJECTIVE: To analyse the immunological and virological effects of treatment interruptions in HIV-1-infected patients with treatment failure and multidrug-resistant virus. METHODS: Drug susceptibility was assessed using Antivirogram and genotypic analysis was based on population and clonal sequencing for 48 patients who had interrupted treatment (> or = 2 months). RESULTS: Treatment interruption resulted in viral load increases (mean 0.7 log 10 copies/ ml; P = 0.0001) and CD4 cell count decreases (mean 89 x 10(6) cells/l; P = 0.0001). A complete shift to wild-type virus at the phenotypic, genotypic and clonal level was observed in 28/45 patients. These patients differed from those that did not show a shift to wild type in baseline CD4 cell counts (192 versus 59 x 10(6) cells/l; P= 0.007) and in the relationship between baseline viral load and CD4 cell count (no correlation versus a significant negative correlation; P= 0.008). Response to re-initiation of treatment fell with increasing viral load [relative hazard (RH) 0.33; P= 0.001] and with increasing total number of drugs with reduced susceptibility (RH 0.51; P = 0.0003); it improved with the number of new drugs received (RH 2.12; P = 0.0002) and a shift to wild type (RH 5.22, P = 0.006). CONCLUSIONS: Changes in surrogate markers suggest that treatment provided benefit in spite of virological failure and resistant virus. Although patients with a shift to wildtype virus responded better in the short term to treatment re-initiation, the long-term effects are not known and the risk of immune deterioration needs to be carefully considered.

Adult↗
PubMed2000

Properties of a fluorescent bezafibrate derivative (DNS-X). A new tool to study peroxisome proliferation and fatty acid beta-oxidation.

The first peroxisome proliferator-activated receptor (PPAR) was cloned in 1990 by Issemann and Green. Many studies have reported the importance of this receptor in the control of gene expression of enzymes involved in lipid metabolic pathways including mitochondrial and peroxisomal fatty acid beta-oxidation, lipoprotein structure [apolipoprotein (apo) A2, apo CIII], and fatty acid synthase. By using radiolabeled molecules, it was shown that peroxisome proliferators bind and activate PPAR. As an alternative method, we developed a fluorescent dansyl (1-dimethylaminonaphthalene-5-sulfonyl) derivative peroxisome proliferator from bezafibrate (DNS-X), a hypolipidemic agent that exhibits an in vitro peroxisome proliferative activity on rat Fao-hepatic derived cultured cells. However, until now, the effect of this new compound on the liver of animals and subcellular localization was unknown. In addition to in vivo rat studies, we present a more efficient large-scale technique of DNS-X purification. Treating rats (DNS-X in the diet at 0.3% w/w) for 6 d leads to a hepatomegaly and a marked increase in liver peroxisomal palmitoyl-CoA oxidase activity. We also developed a method to localize and quantify DNS-X in tissues or cell compartment organelles. The primarily cytosolic distribution of DNS-X was confirmed by direct visualization using fluorescence microscopy of cultured Fao cells. Finally, transfection assay demonstrated that DNS-X enhanced the PPAR alpha activity as well as other peroxisome proliferators do.

Animals↗
PubMed2000

Protein adsorption on nanoporous TiO2 films: a novel approach to studying photoinduced protein/electrode transfer reactions.

We have investigated the use of nanoporous TiO2 films as substrates for protein immobilisation. Such films are of interest due to their high surface area, optical transparency, electrochemical activity and ease of fabrication. These films moreover allow detailed spectroscopic study of protein/electrode electron transfer processes. We find that protein immobilisation on such films may be readily achieved from aqueous solutions at 4 degrees C with a high binding stability and no detectable protein denaturation. The nanoporous structure of the film greatly enhances the active surface area available for protein binding (by a factor of up to 850 for an 8 microns thick film). We demonstrate that the redox state of proteins such as immobilised cytochrome-c (Cyt-c) and haemoglobin (Hb) may be modulated by the application of an electrical bias potential to the TiO2 film, without the addition of electron transfer mediators. The binding of Cyt-c on the TiO2 films is investigated as a function of film thickness, protein concentration, protein surface charge and ionic strength. We demonstrate the potential use of immobilised Hb on such TiO2 films for the detection of dissolved CO in aqueous solutions. We further show that protein/electrode electron transfer may be initiated by UV bandgap excitation of the TiO2 electrode. Both photooxidation and photoreduction of the immobilised proteins can be achieved. By employing pulsed UV laser excitation, the interfacial electron transfer kinetics can be monitored by transient optical spectroscopy, providing a novel probe of protein/electrode electron transfer kinetics. We conclude that nanoporous TiO2 films may be useful both for basic studies of protein/electrode interactions and for the development of novel bioanalytical devices such as biosensors.

Adsorption↗
PubMed1997

Case management: beyond the walls.

Managed care and capitation will become increasingly familiar in the Central Valley of California as managed care arrangements capture more of the marketshare. This type of healthcare environment presents a myriad of opportunities for case management to affect quality and cost outcomes within healthcare organizations. Assessment skills (clinical outcomes), client-provider relationship (member satisfaction), and resource coordination (cost containment) are three key elements underlying the role of the case manager, making the role components congruent with the needs of a managed care population. As payers continue to mandate outcomes measurement, case management beyond the walls or outside the inpatient setting is a technique that will increasingly be used to document that the diverse needs of high-risk patients are met.

California↗
PubMed1996

Self-report of cognition and objective test performance in posttraumatic headache.

The Cognitive Difficulties Scale, a self-report measure of cognitive functioning, was administered to 111 consecutive adult referrals with posttraumatic head pain subsequent to mild to moderate head and/or cervical flexion-extension injuries who were treated at a clinic specializing in head pain and neurological disorders. Factor analysis of the Cognitive Difficulties Scale yielded seven meaningful factors corresponding to the types of memory inefficiencies often associated with neurological dysfunction. Further analyses comparing the Cognitive Difficulties Scale factor scores to objective tests of mental status, memory, and depressed mood demonstrated limited relationships between specific Cognitive Difficulties Scale factor scores and these measures of cognitive performance and behavior. The Cognitive Difficulties Scale appears helpful in assisting this patient population with treatment planning and specific remediation tied to everyday situations.

Activities of Daily Living↗
PubMed1996

Visceral leishmaniasis emerging as an important opportunistic infection in HIV-infected persons living in areas nonendemic for Leishmania donovani.

BACKGROUND: Visceral leishmaniasis is an important infection in patients infected with human immunodeficiency virus and living in areas endemic for Leishmania sp. Leishmaniasis, however, is rarely suspected in patients residing in nonendemic countries. METHODS: Retrospective case analysis of 15 patients with human immunodeficiency virus infection and leishmaniasis treated at seven German clinics. The clinicopathological features and the diagnostic role of biopsy and/or cytology as compared to serology were evaluated. RESULTS: All patients were severely immunocompromised. One patient was first diagnosed at autopsy. One patient with mucocutaneous disease was diagnosed by nasal biopsy. All others had amastigotes detected in bone marrow (13/13), liver (3/3), and gastrointestinal mucosa (4/4). Serology was positive in only 6 or 13. CONCLUSION: Visceral leishmaniasis is an important opportunistic infection in patients with acquired immunodeficiency syndrome and it must be ruled out in every patient with fever and/or pancytopenia and an appropriate travel history. Because serological diagnosis is often insufficient, pathologists must be aware of the association between human immunodeficiency virus infection and leishmaniasis. Diagnosis depends on detection of the parasite in submitted specimens.

AIDS-Related Opportunistic Infections↗
PubMed1994

Expression of trimeric human dUTP pyrophosphatase in Escherichia coli and purification of the enzyme.

In order to rapidly purify human dUTPase, a cDNA fragment that encodes the enzyme was subcloned and expressed using the Escherichia coli plasmid vector pGEX2T. The resulting plasmid expressed high levels of a glutathione S-transferase-dUTPase fusion protein following induction with IPTG. Affinity chromatography was used to purify the fusion protein, and dUTPase was then released from the fusion protein by thrombin treatment. The purified dUTPase has two additional vector-encoded residues at the amino terminus (gly-ser), but they have no apparent effect on the activity of the enzyme since the recombinant dUTPase has catalytic properties similar to those reported for dUTPase purified from human cells (32.3 U/mg, kcat = 25 s-1, Km = 2.6 microM). Enzyme activity was inhibited by 5-mercuri-dUTP and was shown to be sensitive to EDTA. Periodate-oxidized UTP had no effect on the activity of the enzyme, and dTTP caused only slight inhibition. The results of gel filtration experiments are consistent with a homotrimeric subunit composition for dUTPase. The ability to purify human dUTPase from E. coli should allow further characterization of the enzyme and provide material for the screening of potentially useful inhibitors.

Base Sequence↗
PubMed1993

Carboplatin (CBDCA) plus alpha interferon in metastatic non-small cell lung cancer. A Hoosier Oncology Group phase II trial.

Interferons have been shown to increase in vitro cytotoxicity of platinum compounds. The Hoosier Oncology Group has conducted a Phase II clinical trial to determine if interferon alpha-2a (IFN-alpha-2a) given in combination with carboplatin (CBDCA) can increase response rates or survival in patients with metastatic or recurrent inoperable non-small-cell lung cancer. Forty-four patients with no prior chemotherapy and high KPS (80-100) were enrolled. CBDCA 400 mg/m2 was given intravenously on day 1 and IFN-alpha-2a 9 million units was given subcutaneously on days 1, 3, and 5. Treatment was administered every 4 weeks until onset of progressive disease or to a maximum of 4 courses: 37 patients (84%) received at least 2 courses, whereas only 16 (36%) received the full 4 courses. Dose-limiting toxicities were leukopenia (27%) and thrombocytopenia (20%) attributable to CBDCA. Grade 2-3 anemia occurred in 32%. Only 4-7% of patients experienced severe fever, fatigue, or flu-like symptoms attributable to interferon administration. Of 41 patients evaluable for response, there were no complete responses and only 3 (7.3%) partial remissions. The overall median survival was 6 months. The combination of CBDCA and IFN-alpha-2a given in this dose and schedule does not appear to have superior activity compared to CBDCA alone in patients with non-small-cell lung cancer.

Adult↗
PubMed1992

Relationship between volatile fatty acids and magnesium absorption in mono- and polygastric species.

In monogastric animals magnesium is absorbed from the small and large intestine. In ruminants the forestomach system, in particular the rumen, is the most important site of magnesium absorption. Various mechanisms are involved in intestinal magnesium absorption (solvent drag, diffusion, carrier-mediated transport). In the large intestine and rumen an active transepithelial magnesium transport from the mucosal to the serosal side of the epithelium was recently demonstrated. Since in the large intestine and in the rumen, volatile fatty acids (VFA, mainly acetate, propionate, butyrate) deriving from fermentation of carbohydrates represent the major anions, the influence of VFA on magnesium absorption from these parts of the gut was recently investigated. VFA at physiological concentrations stimulated magnesium absorption in both cases. In the rat large intestine VFA enhanced only magnesium absorption by the distal colon, sodium and water absorption remaining unaffected. Both in sheep rumen and in the distal colon of the rat butyrate was most effective in this regard, followed in descending order by propionate and acetate. Sodium absorption by the rat proximal colon and caecum, and by the sheep rumen, was similarly enhanced by VFA. It has been suggested that the latter effect is due to the function of VFA as intracellular proton donators for the Na+/H+ exchanger located in the apical membrane of the epithelial cells. In analogy a Mg2+/H+ exchanger, located in the apical membrane of the epithelium in the distal colon and rumen, is fully consistent with the stimulatory effects of VFA on magnesium absorption at these sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of short-chain fatty acids on calcium absorption by the rat colon.

An in vivo luminal perfusion technique was used to investigate whether short-chain fatty acids influence the absorption of Ca by the rat colon. Na and water absorption were also determined. In the distal colon, acetate and butyrate caused a significant increase in Ca absorption, while the absorption of Na and water were not affected. In the proximal colon, butyrate did not influence Ca absorption, but significantly enhanced Na and water absorption. These results are in part consistent with the presence of a Ca-H exchanger in the apical membrane of the distal colon mediating Ca uptake into the epithelial cell.

Absorption↗
PubMed1990

Effects of short chain fatty acids and K on absorption of Mg and other cations by the colon and caecum.

The influence of short chain fatty acids (SCFA) on Mg, Na, and water absorption was studied in the rat distal colon and caecum using an in vivo luminal perfusion technique. The effect of SCFA on K absorption by the distal colon and the effect of K on Mg absorption by the distal colon and caecum were also investigated. Butyrate (60 mmol/l) or a mixture of SCFA (60 mmol/l acetate, 20 mmol/l propionate, 10 mmol/l butyrate) stimulated Mg and K absorption by the distal colon, while Na and water absorption was not affected. The effect on Mg absorption was pH-dependent. In the caecum, butyrate enhanced Na and water absorption, but not Mg absorption. Acetate (60 mmol/l) did not influence electrolyte absorption by either intestinal segment. K (30 mmol/l) inhibited Mg absorption by the distal colon, but not by the caecum. It is concluded from these findings that SCFA deriving from fermentation of carbohydrates in the large intestine stimulate Mg, K, and Na absorption by delivering protons to Mg++/H+, K+/H+ and Na+/H+ exchangers located in the apical membrane of the epithelium. K seems to inhibit Mg absorption in the colon by affecting a mechanism which does not respond to SCFA.

Acetates↗