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Biomedical subjects

K Klein

Publications and source records attributed to K Klein.

At least 37 records · Page 2Linked to original sources

A comparison of survival at different degrees of hemorrhagic shock in germ-free and germ-bearing rats.

We have previously reported superior survival after one level of hemorrhagic shock in germ-free (GF) rats compared with germ-bearing (GB) rats. The objective of this study was to determine the effect of the GF state on survival at different degrees of hemorrhagic shock. GF and GB rats were bled to a mean arterial blood pressure of 30 mmHg. Shock was terminated after 10, 20, 40, or 80% of the maximum shed blood volume was reabsorbed spontaneously. Both shock time and time to decompensation were significantly longer in GF rats (p < .05). Comparative survival was greater for GF rats at most levels of shock (p < .01). This superiority in survival was greatest at moderate shock levels and decreased at severe shock levels. There may be several reasons for the increased tolerance of GF animals to hemorrhagic shock such as metabolic or immunologic variations. It is hard to avoid the fact, however, that the most notable difference between the GF and GB rat is the presence or absence of bacteria.

Animals

Comparison of the pharmacokinetics of parenteral parathyroid hormone-(1-34) [PTH-(1-34)] and PTH-related peptide-(1-34) in healthy young humans.

The amino-terminal fragments of human PTH [hPTH-(1-34)] and PTH-related peptide [PTHrP-(1-34)] appear to be equipotent in several rodent models. However, continuous i.v. infusions of these peptides to young human volunteers suggested that a 10-fold higher molar dose of PTHrP was required to produce comparable circulating levels of the peptide and biochemical responses similar to PTH. As PTHrP has a wide variety of target tissues in mammalian species and may, therefore, play a paracrine, rather than an endocrine, hormonal role in vivo, we evaluated whether enhanced metabolic clearance of injected PTHrP might explain its apparently reduced potency as a PTH-like hormone. Ten healthy subjects [age, 25 +/- 9 (+/- SD) yr] received in random order either hPTH-(1-34) or hPTHrP-(1-34) given by bolus i.v. injections in a dose of 10.7 nmol. Measurements of plasma immunoreactive peptide indicated a comparable volume of distribution for each, but the apparent t1/2 (8.3 +/- 1.6 min) and plasma clearance (4.0 +/- 1.4 L/min) for hPTHrP were significantly (P < 0.05) accelerated compared to those of hPTH (t1/2, 10.2 +/- 0.5 min; clearance, 2.0 +/- 0.4 L/min). Peak plasma cAMP levels were 9-fold lower in response to hPTHrP (29.5 +/- 19 vs. 190 +/- 63 pmol/L; P < 0.01), and increases in urinary cAMP excretion were 5-fold lower (2.1 +/- 1.1 vs. 11.2 +/- 3.7 nmol/mmol creatinine; P < 0.01). No major differences were observed in the urinary excretion of phosphate, calcium, or sodium between the two peptides. Although hPTHrP-(1-34) has a 2-fold higher MCR than hPTH-(1-34), this may not explain the more than 5-fold lower plasma or urinary cAMP response to PTHrP in humans. The comparable effects of PTH and PTHrP on urinary phosphate, calcium, and sodium may indicate a non-cAMP-dependent pathway for these responses, although the intracellular pool of cAMP generated to either peptide, and thus the local target tissue response, could not be estimated in the present study.

Adult

Multicenter German reference data base for peripheral quantitative computer tomography.

The wide spread use of bone densitometers in Germany and other European countries has required the establishment of a validated reference population data base. A semianthropomorphic forearm cross-calibration phantom (EFP), developed during a concerted research action of the European Union's programme in Biomedical Engineering (COMAC-BME), was used to cross-calibrate the peripheral quantitative computer tomography (pQCT) devices at four German centers participating in the multicenter study. In total, 723 women and 208 men were included in the normal data base. No significant regional differences were found between the data of the different centers. In addition to the manufacturers calibration standard, proper calibration of the pQCT devices could be monitored during collection of the normal female and male data base. As a merit of the COMAC-BME study the measurements obtained with all pQCT devices thus ensured an uniform reference data base for distal radius measurements in Germany.

Adult

Monoclonal antibodies directed against the Epstein-Barr virus-encoded nuclear antigen 1 (EBNA1): immunohistologic detection of EBNA1 in the malignant cells of Hodgkin's disease.

Monoclonal antibodies directed against the Epstein-Barr virus nuclear protein 1 (EBNA1) were used to examine conventional paraffin sections from a series of EBV-associated lymphoproliferative disorders by immunohistochemistry. The presence of latent EBV infection in tumor cells was determined by in situ hybridization for the Epstein-Barr virus early RNAs (EBERs). Of those EBER-positive cases a total of 28 of 40 cases of Hodgkin's disease, 3 of 3 cases of Burkitt's lymphoma, and 8 of 8 cases of human immunodeficiency virus-associated cerebral B-cell lymphoma expressed detectable amounts of EBNA1. In the positive cases, expression was confined to the tumor cells. No reactivity was detected in EBV-negative cases of the above tumors or in 8 cases of EBV-negative cases of large cell anaplastic non-Hodgkin lymphoma. This report provides the first unequivocal evidence for the expression of the EBNA1 protein in the tumor cells of Hodgkin's disease and validates an important reagent with which to analyze the role of EBV in various virus-associated malignancies.

Amino Acid Sequence

Precision of dual X-ray absorptiometry and peripheral computed tomography using mobile densitometry units.

Irrespective of the method used for noninvasive bone mass determination, data comparison between different centers is a major problem as significant interunit variation may occur. We, therefore, have employed mobile densitometry units to reduce interunit variability in two large epidemiologic studies in Germany. Two cars were equipped with either two dual X-ray absorptiometry (DXA) instruments (QDR 1000 Hologic, USA) (car I) or a special purposed scanner for peripheral quantitative computed tomography (pQCT) (XCT 900, Stratec, FRG) (car II). The cars were moved across Germany 11,090 km and 1651 km during the studies over a period of 30 and 7 months, respectively. Precision in vitro was determined using hydroxyapatite phantoms. Forty-eight patients underwent duplicate measurements at the lumbar spine (n = 22) and hip (n = 26) for assessing reproducibility in vivo. Between the two series of scans, the car was moved 63 km. Long-term precision in vitro of the QDR 1000 instruments were 0.41% and 0.59% for BMD with no evidence of machine drift (rate of change per year 0.04% and 0.05%, respectively). Short-term reproducibility in vivo showed a coefficient of variation (cv) of 1.02% for spinal BMD (L2-L4) and 1.72% for femoral neck. Long-term precision in vitro of the pQCT scanner was 0.9%. Our study shows precision in vivo and in vitro and stability of the mobile densitometers similar to that achieved with stationary equipment. In conclusion, mobile densitometry may become a useful tool not only for epidemiologic surveys and clinical trials but also for routine evaluation in less densely populated areas.

Absorptiometry, Photon

The determination of ultrasound velocity in the os calcis, thumb and patella during childhood.

Maximising the accumulation of bone tissue during growth and puberty is one of the most important aims in the prevention of osteoporosis. For prevention studies in children it is necessary to develop methods for skeletal status without radiation. Ultrasonic velocity (speed of sound = SOS) has been proposed as an alternative method. Using a new ultrasonic system (Osteoson K4, Minhorst, Germany), we investigated the reproducibility and age-dependency of SOS in several peripheral bones in 218 children and young adults. Intra-observer (day to day) reproducibility: calcaneus CV = 0.64%, patella CV = 1.18% and thumb CV = 0.43% (n = 25). Inter-observer reproducibility: calcaneus CV = 1.1%, patella CV = 2.48% and thumb CV = 0.62% (n = 16). SOS in thumb and patella increased with age and peaked at 20-25 years. SOS in the calcaneus showed no increase after puberty. Studies in bones from pigs show no dependency of SOS from the thickness of analysed cortical or trabecular bone slices. We conclude that the reproducibility of SOS measurements especially in the thumb is comparable with those of radiation methods. The SOS data in growing, healthy children and the independency from bone dimensions provides more evidence that SOS describes the elastic qualities of the bones.

Adolescent

Pain management for the postoperative patient.

Studies have shown that patients often experience suboptimal analgesia in the postoperative period. In the past decade, a number of advances have been made to improve patient comfort after undergoing surgery. In addition to the obvious desirability of better pain control, adequate postoperative analgesia may decrease the incidence of cardiac and pulmonary complications. Opioid analgesics continue to be the main class of drugs used for postoperative analgesia. However, new methods and routes of administration, including patient-controlled analgesia and epidural and intrathecal drug administration, are currently being used. These modalities, when used appropriately, provide better analgesia, often with fewer side effects than when opiates are given by the traditional intramuscular route.

Analgesics, Opioid

Expression of Epstein-Barr virus nuclear antigen 1,2A and 2B in the baculovirus expression system: serological evaluation of human antibodies to these proteins.

The Epstein-Barr virus encoded nuclear antigens 1,2A, and 2B (EBNA 1, EBNA 2A, and EBNA 2B) were expressed in a baculovirus system. The full length recombinant proteins were recognized by polyclonal rabbit sera and by human sera. An immunofluorescence (IF) test for the differentiation between EBNA 1 and EBNA 2 antibodies in human sera was established with the expressed proteins. None of 55 sera of patients with infectious mononucleosis (IM) had anti-EBNA 1 antibodies while 36 of these sera had anti-EBNA 2A antibodies. Conversely, 47 of 51 sera from EBV-positive healthy carriers had anti-EBNA 1 antibodies and 18 of these sera had anti-EBNA 2A antibodies. The sensitivity and specificity of the EBNA 1 IF for the diagnosis of IM were higher as compared to conventional anti-complement immunofluorescence (ACIF). In the IF test differentiation between type A and type B EBV infection was only possible in sera from the IM patients. An immunoblot (IB) with low amounts of baculovirus expressed EBNA 2A and EBNA 2B antigen was carried out. Twenty-nine of 31 sera from IM patients or from healthy carriers with EBNA 2 antibodies reacted predominantly with EBNA 2A, whereas a known type B serum reacted strongly with EBNA 2B than with EBNA 2A.

Adolescent

Overestimation of osteopenia using standard analysis software for peripheral quantitative computed tomography.

It is well established that measurement of bone mineral density (BMD) can estimate the risk of future fractures. To assess individual fracture risk BMD measurements are compared with a reference range provided by the manufacturer of the respective BMD technology. However, the power of trabecular bone measured by peripheral quantitative computed tomography (pQCT) to predict future fractures has not been shown up to now. We conducted measurements of trabecular bone density (TBD) at the distal radius (pQCT XCT 900, Stratec, Germany) in a sample of 506 healthy white women aged 40-60 years (mean 48) and compared the results with the manufacturer's normal range. We found a remarkable difference in TBD values between our healthy study population and the manufacturer's reference data in all age groups (e.g., age 50-54 years, 143.1 +/- 43.2 mg/cm3 versus 181.1 +/- 39.0 mg/cm3). Compared to the +/- 2 SD limits of the manufacturer's reference range our study population showed mean TBD values that were about 1 SD below the mean of the reference range. About 50% of our healthy cohort were below the -1 SD limit of the reference range. Almost ten times as many normal subjects as expected (22.1%) were found below the -2 SD limit and therefore classified as individuals with increased fracture risk. This overestimation of fracture risk leads to discomfort of the patient, unnecessary therapeutic intervention, and significant costs to the public.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Velocity of ultrasound at the patella: influence of age, menopause and estrogen replacement therapy.

Determination of apparent velocity of ultrasound (AVU) in bone has been proposed as a valuable tool for discriminating between normal and osteoporotic women. We have studied the influence of age, menopause and estrogen replacement therapy (ERT) on AVU at the patella in a large sample of pre- and postmenopausal women. Three hundred and eighteen woman aged 40-60 year participated in the study (112 women were premenopausal, 21 were perimenopausal and 185 were postmenopausal of whom 110 had received ERT for a minimum of 1 year). AVU was determined as the mean of four measurements at each patella using a Signet instrument (Osteo-Technology, Framingham, MA). An age-dependent decline in AVU was observed only after menopause (r = -0.33, p = 0.0055); in premenopausal women there was a slight but not significant decrease in AVU with age (r = -0.12, p > 0.05). AVU was significantly lower in postmenopausal women compared with premenopausal women (1882 +/- .84 m/s vs 1961 +/- 73 m/s, p < 0.05). ERT prevented the menopause-related fall in AVU. There was a significant positive correlation between the duration of ERT and AVU measurements. Our findings demonstrate a pronounced influence of estrogens on AVU at the patella, supporting the concept of a protective role of ERT in bone stability. AVU measurements therefore merit further investigation as an inexpensive method for predicting fracture risk that does not expose the subject to radiation.

Adult

Apparent velocity of ultrasound (AVU) at the patella in comparison to bone mineral density at the lumbar spine in normal males and females.

It has been reported that apparent velocity of ultrasound (AVU) at the patella discriminates as well between osteoporotic and normal subjects as measurement of bone mineral density (BMD) using dual photon absorptiometry. To investigate the relationship between AVU and peak bone mass, we compared AVU (Signet, Osteo-Technology, Framingham, MA) at the patella and BMD (QDR 1000, Hologic, Waltham, MA) at the lumbar spine in a large sample of healthy males and females. The study population consisted of 153 males (aged 20-60 years) and 129 premenopausal females (aged 20-52 years). Vertebral BMD showed no significant difference between males and females (1.03 +/- 0.16 g/cm2 for males vs. 1.07 +/- 0.14 g/cm2 for females, NS), while AVU values were significantly higher in males compared with females (1967 +/- 64 m/s vs. 1938 +/- 76 m/s, P < 0.05). In men there was a significant decrease in BMD with aging (r = -0.27, P < 0.05), in premenopausal females we found no age-related change in BMD. Similarly in males AVU decreased significantly with age (r = -0.2, P < 0.05), whereas in females AVU values showed relative stability over the age range. There was a significant correlation between AVU and BMD (r = 0.36 for males, r = 0.34 for females, P < 0.05). Our study demonstrates only a weak correlation between AVU at that patella and BMD at the lumbar spine, supporting the view that AVU not only reflects bone quantity but possibly also qualitative properties of bone structure. The sex difference in AVU but not in BMD suggests that the trabecular bone at the patella differs significantly from axial trabecular bone. The identical peak BMD at the lumbar spine for young males and females underscores the importance of the menopause for later manifestation of vertebral fractures.

Absorptiometry, Photon

Effect of instructions on isokinetic trunk strength testing variability, reliability, absolute value, and predictive validity.

Although isokinetic strength testing has been in use for more than two decades, and numerous studies have addressed isokinetic performance of the lumbar spine, the effect of instructions on isokinetic trunk strength has not been studied. In a sample of 30 healthy women, this study examined the effect of "high-demand" instructions on lumbar strength performance. High-demand instructions were found to have a substantial positive effect on performance variability, reliability, absolute magnitude, and validity. Under these conditions, isokinetic trunk strength was found to be predictive of performance in a frequent lifting-lowering task.

Adult

Patient education programmes in obstructive airway disease. The Ingelheim Model for promoting health through patient education.

Chronic obstructive airway diseases (COAD) can be regarded as one of the major health problems needing environmental actions and screening programs for early detection and intensive patient education programs to cope with the needs of tertiary prevention. On the basis of our epidemiological study focused on COAD carried out in FRG (sample size August 1988: 63,000 participants) a patient education program has been developed and evaluated. In cooperation with general practitioners and pneumologists the program has been installed at practice and community level. The need for a patient education program has been assessed during the three years of the PNEUMOBIL-Project. It is not just a matter of cutting costs, but to a large extent a matter of the wellbeing of the patients and of reducing side effects to a minimum. The objective of the project can be split into three dimensions: (1) The cognitive aspect. Here significant lack of knowledge has to be overcome. At this point it has to be stated clearly that at the present time the medical community is not able to solve this problem on their own. (2) The psychomotoric aspect. Here the competent use of medication has to be trained. (3) The emotional aspect. The patient has to be motivated and integrated into the therapeutic process in a way that his compliance contributes significantly. The didactical concept consists of modules that can be used in varying sequences according to the needs of the target audience.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Obstruction

[Reproducibility of bone density measurements of the distal radius using a high resolution special scanner for peripheral quantitative computed tomography (Single Energy PQCT)].

Reliable determination of bone loss in the skeletal system depends on the accuracy of bone mineral density (BMD) measurements. We investigated short-term and long-term accuracy in vitro and in vivo using a new, commercially available special-purpose computed tomography scanner (Single Energy Peripheral QCT: XCT 900, Stratec FRG) for BMD measurements. Using a phantom, the long-term accuracy (3 months) in vitro yielded a coefficient of variation (cv) of 0.18%. Repeated measurements in 37 patients showed excellent reproducibility, with a cv of 0.71%. The differentiation into groups of low, average and high trabecular bone density demonstrated values of 0.61%, 0.59% and 0.98%, respectively for cv. BMD determination with pQCT is a high-precision method. It seems to be suitable for detection of trabecular bone loss in the range of the annual decrease in bone mass, provided the forearm is positioned with maximum care.

Bone Density

Glutathione levels during thermal induction of the yeast-to-mycelial transition in Candida albicans.

Glutathione (GSH) levels were directly monitored by reverse phase HPLC during the thermal yeast-to-mycelial induction of Candida albicans. The GSH levels decreased approximately 100-fold within 120 min which corresponded to the time of maximal yeast-to-mold conversion. The yeast to mold conversion was inhibited by 1-p-chlorophenyl-4,4-dimethyl-5-diethylamino-1-penten-3-one (CDDP), a thiol-specific alkylator, which prevented the decline in GSH levels. These results are discussed with respect to the potential involvement of intracellular GSH levels in regulation of the yeast-to-mold dimorphism in Candida albicans.

Candida albicans

Differential gene expression of IFN-alpha and tumor necrosis factor-alpha in peripheral blood mononuclear cells from patients with AIDS related complex and AIDS.

Human PBMC from HIV-1-infected individuals produced ex vivo in response to vesicular stomatitis virus only low amounts of IFN-alpha. This impairment was significant as early as Walter Reed (WR) stage 2; at WR stage 4-5, the production was almost zero. At WR stage 2 of infection, IFN-alpha mRNA was exclusively found in association with polyribosomes, indicating that IFN-alpha gene was transcriptionally inactive under the experimental conditions used. A similar decrease of the level of transcripts as a function of the progression of the disease was also observed for the IFN-gamma mRNA. In contrast, TNF-alpha production was strongly enhanced in PBMC from HIV-1-infected individuals after stimulation with LPS compared to the TNF-alpha production of activated PBMC from healthy donors. Almost parallel with the increase of the level of the transcript for TNF-alpha, the level of TNF-beta increases as well. Data are presented which show that the increased TNF-alpha production is due to a longer half-life of TNF-alpha transcripts in PBMC from infected individuals. These results let us suggest that the up-regulation of TNF-alpha gene expression in PBMC from HIV-infected individuals is controlled predominantly on the posttranscriptional level, whereas transcriptional events regulate the level of IFN-alpha transcripts. This assumption is supported by run-on experiments which revealed that the extent of transcription of TNF-alpha gene is almost identical in nuclei from stimulated PBMC of noninfected and HIV-infected donors, whereas the transcription of IFN-alpha gene is strongly suppressed in nuclei from HIV-infected individuals at WR stages 3 and 6.

AIDS-Related Complex