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Biomedical subjects

K Meyer

Publications and source records attributed to K Meyer.

At least 109 records · Page 6Linked to original sources
PubMed1999

Unopposed neutrophil elastase in bronchoalveolar lavage from transplant recipients with cystic fibrosis.

Large numbers of neutrophils with unopposed neutrophil elastase (NE) proteolytic activity are found in lower respiratory tract secretions from most patients with advanced cystic fibrosis (CF). To determine whether antielastase defenses may be overwhelmed in epithelial lining fluid after lung transplantation, we measured NE activity (cleavage of the specific substrate, MeO-Suc-Ala-Ala-Pro-Val-pNA) in bronchoalveolar lavage fluids (BALF) obtained for surveillance or diagnostic purposes at various intervals (1 mo to 7 yr after transplantation) from 52 recipients who had undergone double or bilateral lung transplantation for end-stage CF. Unopposed NE activity was found in BALF from 14 recipients, most of whom also had >= 10(5) colony forming units (cfu) of Pseudomonas aeruginosa in BALF. Ten of the 14 recipients with unopposed NE in bronchoalveolar lavage (BAL) had developed obliterative bronchiolitis (OB), but only 8 of the 38 subjects without unopposed NE activity had OB (p = 0. 002; Fisher exact test). We conclude that antiprotease defenses in lower respiratory tract secretions of CF patients receiving lung allografts are sufficient in the majority of patients to prevent unopposed NE activity. However, the presence of unopposed NE activity in BAL from lung allografts of patients with CF is associated with progressive, irreversible OB and graft failure.

Adolescent↗
PubMed1999

Four common mutations of the cystathionine beta-synthase gene detected by multiplex PCR and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

BACKGROUND: A deficiency of cystathionine beta-synthase (CBS) is the most frequent cause of homocystinuria. The effect of therapy is related to the underlying CBS genotype, which makes early diagnosis of this genetic defect important. Our aim was to develop a fast and reliable method based on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry for the determination of common mutations of the CBS gene. METHODS: We used MALDI-TOF mass spectrometry to detect four common CBS mutations (G307S, T272M, I278T, and V320A). The method is based on multiplex PCR of exons 7, 8, and 9, followed by single nucleotide extension in the presence of dideoxy NTPs of four primers targeted at the separate mutation sites. The extension products, as well as the 3-hydroxypicolinic acid matrix, were incubated with cation-exchange beads to remove disturbing salt contaminants. RESULTS: The above-mentioned mutations were determined in samples from 12 homocystinuria patients. The MALDI-TOF spectra allowed unambiguous discrimination between primers and extension products (>9 Da) in the mass range between 4500 and 7500 Da. No labeled primers or ddNTPs were required. The genotyping was verified by reference technique. CONCLUSION: Our results demonstrate fast, simple, and unambiguous multiplex genotyping of four common CBS mutations by MALDI-TOF mass spectrometry.

Cystathionine beta-Synthase↗
PubMed1999

Can we assess utility using the patient's own words?

Current methods of utility assessment enable systematic elicitation of patient values in support of medical treatment decision making where interventions involve tradeoffs. Until now, utility assessment protocols have generally employed health care providers' rather than patients' terminology. This study evaluates the feasibility of a protocol that extends traditional methods by using the patient's own words. Fifteen dialysis patients were interviewed with the protocol to elicit individualized multidimensional quality of life (IMQOL) models representing their values. The IMQOL models were then used to assess two modes of dialysis, each with and without complications, as well as the patient's current health. Interview completion rate was 88.2%. Of those completing the interviews, 80% said that they would want the results used to guide decision making in the event of mental incapacity. 53% said the IMQOL model represented their values as well as or better than did traditional utility assessment results.

Adult↗
PubMed1998

Comparison of left ventricular function during interval versus steady-state exercise training in patients with chronic congestive heart failure.

This study sought to assess the safety of interval exercise training in patients with chronic congestive heart failure (CHF) with respect to left ventricular (LV) function. For effective rehabilitation in CHF, both aerobic capacity and muscle strength need to be improved. We have previously demonstrated in both coronary artery bypass surgery and patients with CHF that interval exercise training (IET) offers advantages over steady-state exercise training (SSET). However, because LV function during IET has not yet been studied, the safety of this method in CHF remains unclear. To assess LV function during IET and SSET, at the same average power output, 11 patients with stable CHF were compared with 9 stable coronary patients with minimal LV dysfunction (control group). Using first-pass radionuclide ventriculography, changes in LV function were assessed during work versus recovery phases, at temporally matched times between the fifth and sixteenth minute of IET and SSET. In CHF during IET, there were no significant variations in the parameters measured during work and/or recovery phases. During the course of both IET and SSET, there was a significant increase in LV ejection fraction (5 vs 4 U; p <0.05 each), accompanied by increased heart rate (6 vs 8 beats/min; p <0.05 each) and cardiac output (2.4 vs 1.8 L/min; p <0.01 and p <0.05). In CHF, the magnitude of change in LV ejection fraction during IET was similar to that seen in controls. Both LV ejection fraction and the clinical status in patients with CHF remained stable during IET. Because IET appears to be as safe as SSET with respect to LV function, IET can be recommended for exercise training in CHF to apply higher peripheral exercise stimuli and with no greater LV stress than during SSET.

Exercise Therapy↗
PubMed1998

Lignin monomer composition is determined by the expression of a cytochrome P450-dependent monooxygenase in Arabidopsis.

The phenylpropanoid pathway provides precursors for the biosynthesis of soluble secondary metabolites and lignin in plants. Ferulate-5-hydroxylase (F5H) catalyzes an irreversible hydroxylation step in this pathway that diverts ferulic acid away from guaiacyl lignin biosynthesis and toward sinapic acid and syringyl lignin. This fact led us to postulate that F5H was a potential regulatory step in the determination of lignin monomer composition. To test this hypothesis, we have used Arabidopsis to examine the impact of F5H overexpression. Arabidopsis is a useful model system in which to study lignification because in wild-type plants, guaiacyl and syringyl lignins are deposited in a tissue-specific fashion, while the F5H-deficient fah1 mutant accumulates only guaiacyl lignin. Here we show that ectopic overexpression of F5H in Arabidopsis abolishes tissue-specific lignin monomer accumulation. Surprisingly, overexpression of F5H under the control of the lignification-associated cinnamate-4-hydroxylase promoter, but not the commonly employed cauliflower mosaic virus 35S promoter, generates a lignin that is almost entirely comprised of syringylpropane units. These experiments demonstrate that modification of F5H expression may enable engineering of lignin monomer composition in agronomically important plant species.

Journal Article↗
PubMed1998

Hepatitis C virus core protein represses p21WAF1/Cip1/Sid1 promoter activity.

Hepatitis C virus (HCV) often causes a prolonged and persistent infection, and an association between hepatocellular carcinoma (HCC) and HCV infection has been noted. Recent experimental evidence using a cloned genomic region suggests that the putative core protein of HCV has numerous biological properties and is implicated as a viral factor for HCV mediated pathogenesis. WAF1/Cip1/Sid1 (p21) is the prototype of a family of proteins that inhibit cyclin-dependent kinases (CDK) and regulate cell cycle progression in eukaryotic cells. In this study, we have observed that the HCV core protein represses the transcriptional activity of the p21 promoter when tested separately by an in-vitro transient expression assay using murine fibroblasts (NIH3T3), human hepatocellular carcinoma (HepG2), and human cervical carcinoma (HeLa) cells. A deletion analysis of the p21 promoter suggested that the HCV core responsive region is located downstream of the p53 binding site. A gel mobility shift analysis showed that the HCV core protein does not bind directly to p21 regulatory sequences. Thus, the HCV core protein appears to act as an effector in the promotion of cell growth by repressing p21 transcription through unknown cellular factor(s).

Animals↗
PubMed1998

Inhibition of tumor necrosis factor (TNF-alpha)-mediated apoptosis by hepatitis C virus core protein.

Hepatitis C virus (HCV) putative core protein has displayed many intriguing biological properties. Since tumor necrosis factor (TNF) plays an important role in controlling viral infection, in this study the effect of the core protein was investigated on the TNF-alpha induced apoptosis of human breast carcinoma cells (MCF7). HCV core protein when expressed inhibited TNF-alpha-induced apoptotic cell death unlike the control MCF7 cells, as determined by cell viability and DNA fragmentation analysis. Additionally, HCV core protein blocked the TNF-induced proteolytic cleavage of the death substrate poly(ADP-ribose) polymerase from its native 116-kDa protein to the characteristic 85-kDa polypeptide. Results from this study suggest that the HCV core protein plays a role in the inhibition of TNF-alpha-mediated cell death. Thus, the ability of core protein to inhibit the TNF-mediated apoptotic signaling pathway may provide a selective advantage for HCV replication, allowing for evasion of host antiviral defense mechanisms.

Apoptosis↗
PubMed1998

[Improvement of aerobic capacity in chronic congestive heart failure. Which training method is appropriate?].

Standardized guidelines for exercise training for patients with chronic congestive heart failure (CHF) have not been established. In the past, CHF patients involved in exercise training studies demonstrated a wide range of cardiac and functional impairment, with an ejection fraction between 18 and 35% and a peak VO2 between 12.2 and 25.4 ml/kg/min on average. For determination of training intensity, a VO2 between 40 and 70% of peak VO2 and/or training heart rate between 60 and 80% of peak heart rate was used. There was also a wide range for frequency (between 3 and 7 times per week) and duration of training (between 20 and 60 min per session). For aerobic exercise training only continuous training methods were applied. We have developed a new interval training method which allows intense exercise stimuli on peripheral muscles with minimal cardiac strain. After only three weeks of training, the improvement in aerobic capacity was similar to that reported after longer training periods using continuous methods. To determine work rate for work phases of interval training, a special steep ramp test was developed. By analysis of acute physical responses to this testing procedure and to the interval training, both were proven to be tolerable in CHF patients, even if their ejection fraction is as low as 13%, or peak cardiac index not greater than 1.61/m2/min, and peak VO2 less than 8.5 ml/kg/min.

Chronic Disease↗
PubMed1998

ICAM-1 upregulation in distant tissues after hepatic ischemia/reperfusion: a clue to the mechanism of multiple organ failure.

BACKGROUND/PURPOSE: Endothelial cell adhesion molecules (ECAMs) are felt to play an important role in ischemia/reperfusion (I/R) injury by causing adhesion of leukocytes to endothelial cells. It is possible that ECAMs play a role in multiple organ system failure. ICAM-1 is one of the adhesion molecules that has been shown to be upregulated in response to cytokines. This upregulation leads to leukocyte endothelial cell interaction (adhesion) and to neutrophil infiltration of the affected tissue. The purpose of our study was to measure ICAM-1 expression in the liver and other organs after hepatic ischemia/reperfusion (I/R). METHODS: A laparotomy was performed on 14 Sprague-Dawley rats; 45 minutes of occlusive ischemia to the left lateral lobe was followed by 5 hours of reperfusion. The rat was injected with I125-labeled ICAM-1 MAb and I131-labeled nonbinding MAb (to control for nonspecific accumulation of ICAM-1 MAb). Entire organs were harvested and accumulated activity was measured in each organ. ICAM-1 levels were expressed as percent injected dose per gram of tissue. Control animals underwent sham laparotomy. RESULTS: ICAM-1 was upregulated in the ischemic lobe of the liver, nonischemic lobe of the liver, heart, kidney, intestine, and pancreas. Up-regulation in the lung was not significant. Both the lung and liver had high constitutive levels of ICAM-1. CONCLUSIONS: These data show that (1) significant hepatic upregulation of ICAM-1 after hepatic ischemia/reperfusion and (2) significant ICAM-1 upregulation in other tissues (heart, kidney, and intestine) after hepatic ischemia/reperfusion. The ICAM-1 upregulation in distant organs is likely mediated by cytokines such as tumor necrosis factor (TNF). These data show that leukocyte endothelial cell interactions in distant organs may be mediated by hepatic ischemia/reperfusion. This is a possible explanation for how failure of one organ can lead to failure of others in multiple organ system failure.

Animals↗
PubMed1998

Performance of the SE-9000 automated haematology analyser in a laboratory serving a haematological oncology unit.

The performance of the SE-9000 automated haematology analyser in a laboratory receiving a high number of abnormal specimens from haematological oncology patients was assessed according to formal protocols for the evaluation of blood cell counters. Linearity over a useful working range, precision in clinically important ranges and negligible carry-over were demonstrated in this group of patient samples confirming the results of previous investigators. The comparability of instrument derived differential leucocyte counts from both normal and distributionally abnormal samples with those obtained by visual microscopy using the NCCLS H-20 A protocol was very good. The sensitivity of flags for the detection of immature granulocytes and myeloid blast cells was high and this can be attributed to the incorporation of a new measuring channel (Immature Myeloid Information or IMI channel). The number of unrecognized abnormalities was low and when compared with the poor sensitivity of the routine 100-cell visual differential leucocyte count, the analyser was judged suitable for monitoring patients with haematological malignancies. The performance of flags such as 'left shift' and 'atypical lymphocytes' can be improved by taking into consideration distributional abnormalities such as neutrophilia and lymphocytosis. The trigger level for these flags should be adapted to the clinical need particularly in cases of neutropenia following chemotherapy, and in lymphoproliferative disorders and infection.

Adult↗
PubMed1998

Total knee and hip arthroplasty in haemophilic patients.

UNLABELLED: We evaluated the long-term results of three total hip and nine total knee arthroplasties in nine haemophilic patients with disabling pain and end-stage arthropathy. These patients have been followed over a period of 2-12 years (mean 6.9). One patient had a post-operative haematoma, which was evacuated; two patients required manipulation of the knee because of a limited range of motion. There were no infections. At follow-up, all but two patients were completely free of pain; two patients had occasional pain. The functional improvement was impressive with an average increase in the knee score from 37 to 80 points post-operatively. The hip score increased from 36 to 85 points. The range of motion was increased in seven joints, unchanged in two joints and decreased in three. One total hip arthroplasty was revised after 9 years for aseptic loosening. One total knee demonstrated nonprogressive radiographic evidence of aseptic loosening. Median consumption of coagulation factor concentrate in severe haemophiliacs decreased from 47.00 U yr-1 (range 16.000-144.000) before surgery, to 25.000 U yr-1 (range 18.000-132.000) at 2 years after surgery. CONCLUSION: Hip and knee arthroplasty is a valuable option in symptomatic haemophilic patients with disabling arthropathy, in order to obtain pain relief and functional improvement. It is associated with a low rate of complications and may reduce the need for substitution of factor VIII and IX.

Adult↗
PubMed1998

Delayed VO2 kinetics during ramp exercise: a criterion for cardiopulmonary exercise capacity in chronic heart failure.

PURPOSE: Kinetics of VO2 at onset of constant work rate exercise was previously shown to be slowed in patients with chronic heart failure (CHF) compared with that in healthy normals. Because bicycle ergometry with ramp protocol is usually used for exercise testing with CHF patients, it would be of practical importance if it can be shown that a delay in the time interval of linear increase of VO2 (TILIV) to work rate occurs after beginning ramp exercise. Data of central hemodynamics (CHF) and noninvasive cardiopulmonary parameters (CHF, normals) should also correlate with VO2 delay time if this parameter is related to cardiopulmonary exercise capacity. METHODS: Fifteen males with CHF (mean +/- SEM: age 52 +/- 2 yr; ejection fraction 32 +/- 4%; peak cardiac index 3.9 +/- 0.3 L x m(-2) x min(-1)) and 28 healthy males (50 +/- 1 yr) were assessed. During ramp bicycle ergometry (3 min unloaded, work rate increments of 12.5 W x min(-1)), VO2 was measured breath by breath. RESULTS: After the onset of ramp exercise, there was a difference in the TILIV between patients and normals (83.7 +/- 3.6 vs 66.8 +/- 2.9 s; P < 0.001). Significant differences between both groups were also found for VO2 at ventilatory threshold (VT) (10.1 +/- 0.1 vs 15.2 +/- 0.7 mL x kg(-1) x min(-1); P < 0.0001), VO2 at VT relative to predicted VT (58 +/- 4 vs 97 +/- 4%; P < 0.0001), peak VO2 (13.2 +/- 1.0 vs 34 +/- 1.4 mL x kg(-1) x min(-1), P < 0.001), and increase of systolic blood pressure (36 +/- 7 vs 71 +/- 5 mm Hg; P < 0.0001). In CHF, the TILIV correlated significantly with peak cardiac index and VO2 at VT (r = -0.71; P < 0.005 each), relative value of VO2/kg at VT (r = -0.61; P < 0.03), peak VO2/kg (r = -0.63; P < 0.01), and increase of systolic blood pressure (r = -0.52; P < 0.02). In the normals only VO2/kg at VT correlated significantly with TILIV (r = -0.41; P < 0.03). In patients, stepwise regression analysis identified three predictors which could explain 79% of the variance of TILIV: VO2/kg at VT (r2 = 0.51), peak cardiac index (r2 = 0.20), and peak VO2/kg (r2 = 0.08). CONCLUSION: TILIV, determined at the onset of ramp exercise, is prolonged in CHF patients compared with that in normals and reflects severity of functional impairment because of reduced cardiac index and aerobic capacity. TILIV can provide information about changes in cardiopulmonary exercise capacity and thus can be used for follow-up and treatment studies in CHF.

Cardiac Output, Low↗
PubMed1998

Physiological and pathological aspects of exercise left ventricular function.

Measures of left ventricular function during exercise provide information that is more accurate than the exercise ECG in the diagnosis of coronary artery disease, supportive of the data provided by myocardial perfusion studies, and of great prognostic significance. We review basic methods for evaluating left ventricular function during exercise and responses to various types of exercise, including incremental exercise and exercise training conditions. Additionally, we review changes in both incremental exercise test responses and responses to training in various pathological conditions. Case reports are included to illustrate the utility of measuring left ventricular function during exercise.

Coronary Circulation↗
PubMed1998

Flow cytometric identification of myeloid disorders by asynchronous expression of the CD14 and CD66 antigens.

Using a multiparameter flow cytometry assay enumerating cells positive for CD13, CD14 and CD66 antigens, we determined the asynchronous CD14/CD66 co-expression in unselected bone marrow and peripheral blood samples with suspected malignant blood disorders. CD14/CD66 co-expression > or = 5% were found in 131/691 bone marrow samples. Only 55 of these exhibited an identifiable population in 2-parameter flow cytometry histograms. Of the 55 samples 43 (78%) came from patients with myeloid disorders; e.g. 11 with myelodysplastic syndromes, 15 with chronic myeloproliferative disorders and 17 with acute myeloid leukaemia. Only one of these 17 cases was a de novo case, while 8 were secondary to another malignant haematological disease and 8 were from the period after cytoreductive therapy. Notably, CD14/CD66 co-expression patterns were related to disease categories; e.g. in chronic myelomonocytic leukaemia and acute myeloid leukaemia following a dysplastic phase the co-expression displayed two subsets in peripheral blood, low-avidity CD14 and low-avidity CD66, respectively. The latter disease category also exhibited these 2 subsets in bone marrow. In all other cases, the CD14/CD66 co-expression in bone marrow was heterogeneous. In conclusion, abnormal CD14/CD66 co-expression might be a valuable parameter in defining asynchronous myelopoiesis in malignant myeloid disorders, especially myeloproliferative disorders and secondary acute myeloid leukemias.

Antigens, CD↗
PubMed1998

Practical aspects of managing preschool children with type 1 diabetes.

Day-to-day variations in diet and physical exercise, large variations in the glucose response to small changes in insulin doses, and high insulin sensitivity are characteristic of preschool children with diabetes. Hence, difficulties in achieving adequate metabolic control and stable glycaemia in preschool children are common. In addition, hypoglycaemic episodes tend to be frequent and severe in this age group. Problems identifying and treating hypoglycaemia present an additional challenge for the diabetes team and for the family caring for the young child with diabetes. Specific glucose targets are provided for this age group: premeal levels of 6-12 mmoll(-1)(110-220 mg dl(-1)) with bedtime levels above 8 mmoll(-1)(140 mg dl(-1)). It is important to note that children who suffer severe hypoglycaemic events at a young age show evidence of subtle cognitive deficits when tested during adolescence. The question of whether or not the years before pubertal onset contribute less towards the development of diabetes-related microvascular complications than do the years starting with the onset of puberty remains controversial. Twice-daily or multiple insulin injections, dietary adjustments and considerations, home blood-glucose monitoring, family education, support groups and 24-h hotline information facilities can help to achieve good metabolic control without severe hypoglycaemia in the preschool child. In general, good metabolic control without severe hypoglycaemia can be achieved using frequent counselling and a caring team approach.

Aging↗
PubMed1998

Functional role of hepatitis C virus chimeric glycoproteins in the infectivity of pseudotyped virus.

The putative envelope glycoproteins of hepatitis C virus (HCV) likely play an important role in the initiation of viral infection. Available information suggests that the genomic regions encoding the putative envelope glycoproteins, when expressed as recombinant proteins in mammalian cells, largely accumulate in the endoplasmic reticulum. In this study, genomic regions which include the putative ectodomain of the E1 (amino acids 174 to 359) and E2 (amino acids 371 to 742) glycoproteins were appended to the transmembrane domain and cytoplasmic tail of vesicular stomatitis virus (VSV) G protein. This provided a membrane anchor signal and the VSV incorporation signal at the carboxy termini of the E1 and E2 glycoproteins. The chimeric gene constructs exhibited expression of the recombinant proteins on the cell surface in a transient expression assay. When infected with a temperature-sensitive VSV mutant (ts045) and grown at the nonpermissive temperature (40.5 degrees C), cells transiently expressing the E1 or E2 chimeric glycoprotein generated VSV/HCV pseudotyped virus. The resulting pseudotyped virus generated from E1 or E2 surprisingly exhibited the ability to infect mammalian cells and sera derived from chimpanzees immunized with the homologous HCV envelope glycoproteins neutralized pseudotyped virus infectivity. Results from this study suggested a potential functional role for both the E1 and E2 glycoproteins in the infectivity of VSV/HCV pseudotyped virus in mammalian cells. These observations further suggest the importance of using both viral glycoproteins in a candidate subunit vaccine and the potential for using a VSV/HCV pseudotyped virus to determine HCV neutralizing antibodies.

Animals↗
PubMed1998

The Early vs Late Infantile Strabismus Surgery Study: do sources for bias exist in this non-randomised trial? Early vs Late Infantile Strabismus Surgery Study Group.

BACKGROUND: The Early vs Late Infantile Strabismus Surgery Study Group investigates whether early or late surgery is preferable in infantile convergent strabismus, in a non-randomised, prospective, multicentre clinical trial. The current state of the study after end of recruitment is reported here, focusing on the question of possible sources for bias in this non-randomised trial. METHOD: The prognostic factors were analysed at baseline in order to check for imbalances between the two treatment groups. Reasons for possible differences are discussed. RESULTS: There is no evidence for clinically relevant inhomogeneities between the two groups concerning the distribution of the three prognostic factors spherical equivalent, degree of amblyopia, and limitation of abduction. The fourth prognostic factor, horizontal angle of squint, differs significantly between the two groups. CONCLUSION: In the analysis of the final results we may have to account for differences in angle of squint at baseline by its inclusion as a covariate or by stratification.

Age Distribution↗