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Biomedical subjects

E Keller

Publications and source records attributed to E Keller.

At least 181 records · Page 10Linked to original sources

Androgen receptor: an overview.

The action of androgens in regulating development and growth is mediated by androgen receptor (AR). AR is a member of the steroid hormone receptor superfamily, a class of receptors that function through their ability to regulate the transcription of specific genes. The AR is located in various target tissues, with its levels and activity altered with the onset of various cellular events (e.g., sexual development, malignant transformation). The modulation of AR levels occurs through a number of mechanisms, including transcription, and is regulated by various factors (e.g., androgens). The ability of AR to modulate gene transcription is through its interaction with specific DNA sequences located near or within the target gene promoter. The importance of the AR in reproductive physiology has been emphasized by the finding of AR mutations, leading to a variety of disorders, including testicular feminization syndrome. In this article, we review the structure and function of AR and the role AR plays in the function of the mammalian system.

Animals↗

Treatment of pelvic abscesses: value of one-step sonographically guided transrectal needle aspiration and lavage.

OBJECTIVE: The percutaneous treatment of pelvic abscesses has traditionally involved the placement of drainage catheters via a transgluteal, transrectal, or transvaginal route. These procedures are painful and prolonged. The goal of this study was to demonstrate the effectiveness of a one-step, single-puncture method for draining pelvic abscesses by use of a transrectal sonographically guided needle for aspiration and lavage instead of a two-step Seldinger technique for catheter placement. SUBJECTS AND METHODS: Thirty-three pelvic abscesses in 24 patients were drained by use of transrectal ultrasound guidance. All abscesses were initially seen on transrectal sonograms or CT scans and ranged from 2 to 11 cm in diameter. Abscesses were located in the prostate (n = five), seminal vesicles (n = five), pouch of Douglas (n = 21), and interloop (between bowel loops) (n = two). Causes of pouch of Douglas (cul-de-sac) abscesses included appendicitis (n = two), Crohn's disease (n = two), diverticulitis (n = three), trauma (n = six), HIV infection (n = two), complications of sigmoidectomy (n = one), complications of colectomy (n = one), pelvic inflammatory disease (n = two), and severe prostatitis (n = two). Interloop abscesses were attributable to HIV infection (n = one) and lymphoma (n = one). The procedure was performed without a cleansing enema or local anesthesia and required less than 30 min. An 18-gauge needle was inserted transrectally into the abscess cavity under transrectally guided sonography. The fluid collection was completely aspirated, and the cavity was lavaged with saline. Administration of antibiotics for 7-21 days, rather than prolonged catheter drainage, was used to treat residual infection. Resolution was documented after 7 days by sonography or CT examination. RESULTS: Transrectal aspiration was successful in treating 28 (85%) of the 33 pelvic abscesses in 21 (88%) of the 24 patients. Failure occurred in three patients, two with multiple abscesses and one with an enteric fistula for whom surgical drainage was subsequently required. The volume of aspirates ranged from 5 to 220 ml. There were no complications. CONCLUSION: Transrectal sonographically guided needle aspiration-lavage offers a one-step method for treating pelvic abscesses that does not require catheter placement or prolonged drainage. The procedure produces minimal discomfort and essentially no complications. Our results show that transrectal sonographically guided needle aspiration combined with antibiotic therapy is an effective treatment for pelvic abscesses.

Abscess↗

Evaluation of diagnostic criteria for analgesic nephropathy in patients with end-stage renal failure: results of the ANNE study. Analgesic Nephropathy Network of Europe.

It was found that in Belgium, renal imaging techniques, demonstrating a decreased renal mass of both kidneys combined with either bumpy contours or papillary calcifications, were the only methods to reliably diagnose analgesic nephropathy (AN) in patients with end-stage renal failure. However, these criteria were selected in an area with a high prevalence of this disease (15.6% of the dialysis population at December 1990). To evaluate the criteria selected to diagnose AN in populations with lower or unknown prevalences of AN, the Analgesic Nephropathy Network of Europe (ANNE) was formed, consisting of 23 dialysis units from 14 European countries and Brazil. During 1991-1992, 598 new patients with equivocal diagnosis of renal disease (excluding biopsy-proven glomerulonephritis, polycystic disease, diabetic nephropathy and other systemic diseases) and who began renal replacement therapy in the ANNE centres were evaluated by a short questionnaire and two renal imaging techniques: sonography and either tomography or computed tomography (CT) scan. A comparison of 82 abusers (daily use of analgesic mixtures for at least 5 years) and 495 controls corroborated the excellent diagnostic performance of the renal imaging techniques for AN. We recommend the use of these renal imaging criteria in all patients without a clear renal diagnosis in order to obtain a more reliable insight into the magnitude of the AN problem in different countries.

Adult↗

[Turbo-spin-echo MR imaging of the brain at 0.5 T].

Turbo-spin-echo (TSE) imaging is a fast technique, which provides true spin-echo contrast in a definitely shorter scan time than conventional spin-echo (SE). Clinical studies at 1.5 T show that TSE is a valuable alternative to SE and will ultimately replace time-consuming T2-weighted SE imaging for examinations of the brain and brainstem. Besides the reduction of scan time, TSE is less sensitive to motion artefacts. A slight decrease of susceptibility effects of 1.5 T can be a disadvantage in the detection of old haemorrhagic lesions and calcifications. In these cases the gradient-echo sequence will remain the most sensitive. TSE allows a greater flexibility of examination strategies, including several orientations, strongly T2-weighted images and high spatial resolution (HR) MRI. HR MRI using thin slices (1-3 mm), a small field of view and a 512 image matrix yields detailed information about small anatomical regions (e.g. the pituitary fossa, cavernous sinus, internal auditory canal and brainstem) and permits the delineation of specific cranial nerves. In this study TSE was utilized at 0.5 T field strength in order to assess whether the advantages of TSE hold for midfield systems. Preliminary results in imaging of the brain and brainstem are very promising.

Adolescent↗

Single dose kinetics of piperacillin during continuous arteriovenous hemodialysis in intensive care patients.

Piperacillin (Pi) kinetics in patients with acute renal failure treated by continuous arteriovenous hemodialysis (CAVHD) are not known. Therefore, dosing regimens have been based on kinetic data derived from patients with chronic renal failure and principal pharmacokinetic considerations [Reetze-Bonorden et al. 1993]. From these estimations it has been predicted that approximately 30% of the dose of Pi is removed by CAVHD (dialysate/ultrafiltrate (D/UF) flow rate 1.5 liter/hour). To confirm this estimate single dose (4g i.v.) Pi kinetics were studied in 12 intensive care patients with anuric acute renal failure due to septicemia treated by CAVHD. Pi plasma and D/UF levels were measured by HPLC. Sieving/Saturation of Pi in the D/UF was 0.71 +/- 0.21 (+/- SD). With a mean D/UF flow rate of 20.4 +/- 1.5 ml/min, the mean extracorporal clearance (Clextra) was 12.2 +/- 1.0 ml/min and accounted for 29% (range 14-48%) of total body clearance (ClB = 47.1 +/- 22.3 ml/min). In 7 out of 12 patients the fraction of the dose eliminated by CAVHD reached a significant value above 25%. The mean volume of distribution (Vd) and elimination half life (t1/2) were 25.8 +/- 3.8 liter and 7.4 +/- 2.9 hours, respectively. In conclusion the extent of extracorporal elimination of Pi by CAVHD was well in agreement with the estimation previously published. In intensive care patients with acute renal failure on continuous hemodialysis Pi dosing should take into account the possibly significant elimination of Pi. The usual dose for anuric patients may be increased by 50% to avoid underdosing in these critically ill patients.

Acute Kidney Injury↗

[Studies on sexual development, sexual behavior and ability to experience sex of young women with Ullrich-Turner syndrome].

In this investigation 25 female patients were included with the Turner syndrome (TS). From the 25 patients 6 had spontaneous menstruations, 19 had menstruations only after a hormonal stimulation. In a semi-structured interview the patients were questioned about their sexual activities, behavior and orgastic capacity. The findings were related to a matched normal female population. Moreover an analysis of personality traits by means of the Freiburger Persönlichkeitsinventar [FPI], the Giessen Test [GT], and a questionnaire on education styles of parents [EMBU] has been undertaken. The endocrine profile of the patients with induced menarche showed an elevated value of LH and FSH in serum, and a low level of estradiol. The sexual development of all patients was normal during the prepubertal phase. However the biological puberty was delayed by three years in the study patients, in relation to a normal population. Each of these women had a normal female identity and was heterosexual oriented. In concordance with the literature, patients who were substituted too late, showed defined deficits in their psychic well being, as well as in their social and psychosexual functioning. These deficits only were significant in relation to delayed menarche, but not to chronological age, gynecological age, karyotype, body height or parental education style. Therefore, an early and adequately dosed hormonal intervention and a consequently and regularly performed substitution therapy with sexual steroids has to be undertaken beside the well known intervention with growth hormone.

Adolescent↗

Continuous non-invasive blood pressure monitoring by brachial artery displacement method in high-risk surgical patients.

Continuous non-invasive blood pressure (CNBP) measurements were compared to invasive radial artery pressure recordings in 26 patients with cardiac, vascular and/or pulmonary disease. Patients were studied during general anaesthesia (n = 6), regional anaesthesia (n = 10), or combined technique (n = 10) for abdominal or transurethral surgery. CNBP was obtained from a cuff placed around the upper arm and simultaneously compared to invasive pressure from the ipsilateral radial artery. A CNBP device (7001 Cortronic) used intermittent oscillometric measurement for calibration. Through a cuff continuously inflated to a pressure of 20 mmHg, a microprocessor-controlled electro-pneumatic acquisition system sensed displacements of the brachial artery wall. Amplified, digitally converted, filtered and transformed data were displayed as a continuous pulse pressure waveform and digital pressure values on the screen. The CNBP method functioned without disturbances before surgery in all patients. Intra-operative use of electrocautery or a spontaneous occurrence of warning on the screen repeatedly triggered oscillometric recalibration, hence CNBP measurements were discontinued in nine patients. Coefficients of correlation (r) of all invasive and CNBP pairs (n = 1111) were 0.68, 0.58 and 0.70 for systolic, diastolic, and mean blood pressures, respectively. Prediction errors (bias, mean +/- SD) were -13.6 +/- 22.5 mmHg (on average CNBP < invasive pressure) for systolic, +13.0 +/- 12.4 mmHg (CNBP > invasive pressure) for diastolic and +5.0 +/- 13.9 mmHg (CNBP > invasive pressure) for mean CNBP, as compared to radial artery pressure values. Absolute errors (precision) were 25.3 +/- 9.4 mmHg for systolic, 17.4 +/- 4.5 mmHg for diastolic, and 13.9 +/- 4.6 mmHg for mean CNBP. During anaesthesia induction (n = 672) the difference between consecutive measurements (trend of pressure changes) with invasive and CNBP method exceeded 20 mmHg in 90 (13.3%) instances for systolic, in 33 (4.9%) instances for diastolic, and in 45 (6.6%) instances for mean blood pressure. In conclusion, the CNBP method by brachial artery wall displacement failed to measure the blood pressure reliably and to display the trend of pressure changes correctly during anaesthesia induction. In its present form this CNBP method should not replace invasive blood pressure monitoring in high-risk patients neither for anaesthesia induction nor during non-thoracic surgical procedures.

Abdomen↗

Mechanosensitivity of voltage-gated calcium currents in rat anterior pituitary cells.

Sensitivity of voltage-activated calcium currents to flow-induced mechanical stress was examined in enriched populations of rat anterior pituitary somatotrophs. Voltage-activated calcium currents were recorded with the whole-cell configuration of the patch-clamp technique. Pituitary cells were exposed to flow (from pipettes) which was produced by a hydrostatic pressure of about 3 cmH2O. In 92% of the cells studied (n = 87 cells) flow reduced the amplitude of both low voltage-activated (LVA) and high voltage-activated (HVA) calcium currents. These effects of flow on calcium currents did not result from changes in either seal resistance or leak conductance of the cell and were dependent on the magnitude of flow. The effect of flow is selective. We found that LVA calcium currents were substantially more sensitive to flow than HVA calcium currents. Under constant flow conditions, LVA calcium currents were reduced by 57.6 +/- 29.6% (S.D.), whereas HVA currents (recorded from the same cells) were reduced by only 17.8 +/- 15.9% (S.D.). The effects of flow on calcium currents were associated with effects on their related calcium tail currents. Slowly deactivating calcium tail currents were reduced by 75.3 +/- 25.6% (S.D.), whereas rapidly deactivating calcium tail currents were reduced by 29.1 +/- 14.4% (S.D.). The effect of flow on calcium currents was not associated with any significant shift in the activation curves of the calcium currents (voltage range -60 to +30 mV), suggesting that the effect of flow is not voltage dependent. The effect of flow is not dependent on activation of calcium currents during the exposure to flow. Calcium currents which were evoked immediately after cessation of the exposure to flow were reduced in amplitude and recovered to control values. Possible mechanisms underlying the flow effect and possible physiological relevance of the effect on pituitary cells are discussed.

Animals↗

HLA class II genes and antibodies against recombinant U1-nRNP proteins in patients with systemic lupus erythematosus. SLE Study Group.

To investigate a possible involvement of HLA-class II alleles in the genetic predisposition for the formation of anti-U1-nRNP antibody-in systemic lupus erythematosus (SLE), genomic DNA of 178 patients was typed for the DRB1, DQA1 and DQB1 alleles using a polymerase chain reaction (PCR) and non-radioactive-oligonucleotide typing. Antibodies against recombinant U1-nRNP proteins (U1-A-, U1-C- and 70K-protein) were determined by ELISA. Anti-U1-C antibody was found in 26 (14.7%), anti-U1-A in 34 (19.2%) and anti-70K in 17 (9.6%) patients. A joint occurrence was observed for these antibodies against the recombinant U1-nRNP proteins: anti-U1-C and anti-U1-A antibodies occurred together more frequently than alone and than together with anti-U1-70K antibodies. The frequency of DRB1*04 was slightly increased in the patients with anti-U1-C as compared to the patients without anti-U1-C (P < 0.05, Pcorr = n.s., RR = 2.4). The DQA1*0301 allele, which is in linkage disequilibrium with DRB1*04, is found more frequently in anti-U1-C-positive than in antibody-negative patients. The DQB1*0303 allele, detected in 12 of 176 SLE patients, was absent in the patients with any of the antibodies against the U1-nRNP proteins. All these deviations may be due to chance alone. We concluded that the presence of antibodies against recombinant U1-nRNP proteins was not significantly associated with any HLA DRB1, DQA1 and DQB1 allele in our group of SLE patients.

Alleles↗

Polymorphism in the upstream regulatory region of DQA1 genes and DRB1, QAP, DQA1, and DQB1 haplotypes in the German population.

Polymorphism in the URR of the MHC class II DQA1 gene defines ten different alleles named QAP. Oligotyping for the alleles of DRB1, QAP, DQA1, and DQB1 have been performed in 210 unrelated healthy controls from Germany. Moreover, 83 HTCs from the Tenth IHWS have been tested. Four point loci haplotypes (DRB1, QAP, DQA1, and DQB1) have been analyzed in the unrelated healthy population sample. Computer analysis of the linkage disequilibria leads to the conclusion that QAP alleles are in strong linkage disequilibrium with alleles either the DQA1 or the DRB1 locus. One typical ("common") haplotype was found to be associated with each DRB1 allele in the majority (86%) of the tested persons. Apart from that, 25 other less frequent ("unusual") haplotypes, with an overall frequency of 14% have been defined. Some of these "unusual" MHC class II haplotypes were found to differ only in the regulatory alleles of DQA1 (QAP alleles) while they are identical for the alleles coding for structural elements (DRB1, DQA1, and DQB1). Most of the "unusual" haplotypes were found to carry HLA-DQ6. Assuming that "unusual" (= rare) haplotypes have arisen from "common" (= frequent) haplotypes by point mutation and recombination, we propose the existence of three recombination sites in the MHC DR-DQ region: one between DRB1 and QAP, the second between QAP and DQA1, and the third between DQA1 and DQB1.

Alleles↗

Pharmacokinetics of gabapentin in subjects with various degrees of renal function.

The pharmacokinetics of oral gabapentin (400 mg) was studied in normal subjects and in subjects with various degrees of renal function. Sixty subjects participated in this three-center study. None of the subjects were receiving hemodialysis. Plasma and urine samples were collected for up to 264 hours after dosing, and concentrations of gabapentin were determined by high performance liquid chromatography. Apparent oral plasma clearance (CL/F) and renal clearance (CLR) of gabapentin decreased and maximum plasma concentration, time to reach maximum concentration, and half-life values increased as renal function diminished. Gabapentin CL/F and CLR were linearly correlated with creatinine clearance. Total urinary recovery of unchanged drug was comparable in all subjects, indicating that the extent of drug absorption was unaffected by renal function. There was no evidence of gabapentin metabolism even in subjects with severe renal impairment. In summary, impaired renal function results in higher plasma gabapentin concentrations, longer elimination half-lives, and reduced CL/F and CLR values. Based on pharmacokinetic considerations, it appears that the dosing regimen of gabapentin in subjects with renal impairment may be adjusted on the basis of creatinine clearance.

Acetates↗

Molecular analysis of CYP21 gene mutations carried on HLA-B14 positive haplotypes.

HLA-B14 positive haplotypes have increased frequencies in a group of patients with puberty disorders, IgA deficiency and cancer of the ovary. Clinical investigations demonstrated that all these patients have high values of 170H progesteron after the ACTH test which suggests an alterated function of 21 hydroxylase enzyme. In order to investigate whether these B14 positive haplotypes carry the same CYP21 mutation in the various diseases and controls, we have amplified by polymerase chain reaction (PCR) the sections of CYP21B gene which include amino acid positions 172 and 281 where typical mutations are known to occur in 21 hydroxylase deficiency. The presence or absence of the defined mutations was tested by oligonucleotide hybridization using oligonucleotides, labelled with DIG-ddUTP, designed to hybridize with the mutated or with the normal sequence. It was found that regardless of whether the subject tested was a patient or a healthy control the mutation at position 281 was found in all cases carrying HLA-B14, DR1 haplotype. Interestingly, this mutation does not seem to be in association with HLA-B14, DR7 haplotype. These findings suggest that CYP21 gene plays a role in all these differing diseases although it must be stressed that there may be alternative explanations for the observed data.

Adolescent↗

Measurement of subcellular Ca2+ redistribution in cardiac muscle in situ: time resolved rapid freezing and electron probe microanalysis.

To directly assess the physiological roles of sarcoplasmic reticulum (SR) and mitochondria (MT), we have utilized energy dispersive electron probe microanalysis (EPMA) on ultrathin freeze-dried cryosections from isolated papillary muscles, rapidly frozen at precise time points of the contractile cycle. Using this approach, we can detect redistribution of subcellular Ca2+ during the cardiac contractile cycle. Changes in Ca2+ of less than 1.0 mmol/kg dry wt can be detected. By determining the variability of the Ca2+ measurements in preliminary experiments, we have also demonstrated that it is possible to optimize experimental design, i.e., to predict the number of animals per treatment group and the number of X-ray spectra per animal that are required in order to detect a specified Ca2+ difference. Quantitative EPMA of rapidly frozen contracting papillary muscle has also allowed us to correlate the Ca2+ content of SR and MT with the contractile state of the muscle. Our results show a decrease of 40% in the amount of Ca2+ stored in the junctional SR during a cardiac muscle twitch, thus providing direct evidence for a role of the SR as a primary site of Ca2+ release. In addition, we have demonstrated dissociation between MT Ca2+ uptake and activation of regulatory enzymes, such as pyruvate dehydrogenase, indicating that MT Ca2+ uptake is not required for activation of MT metabolism.

Animals↗

[Screening for a growth disorder using the Dr. Keller precision measuring instrument and system].

The regulation of growth is as complex process involving the interaction of a number of genetic, hormonal, psychosomal, and environmental factors. Abnormal growth is an alarming sign for the worsening of health. Therefore is it necessary to provide exact and quick information about the growth of the child. With the body length device "System Dr. Keller" is it possible to collect 1. exact data about the actual height of a child, 2. information about the normal range of height for the chronological age of a child, 3. information about abnormal height (< 3., > 97. percentile) of a child. These informations are visible exclusively by application of the "System Dr. Keller". With use of this unique system and the data of corresponding national growth studies it will be possible to screen the whole population by paediatricians, general practitioners, school doctors, health care centers, outpatient departments and hospitals. While normal growth usually represents health, growth disorders should stimulate doctors to exclude possibly underlying pathological processes.

Adolescent↗

Lymph node staging in 872 patients with carcinoma of the stomach and the presumed benefit of lymphadenectomy. German Stomach Cancer TNM Study Group.

The incidence of surgically suspected and microscopically proved lymph nodes from adenocarcinoma of the stomach and the results of systematic lymphadenectomy have been studied and correlated to survival rate of 99.4 percent at a follow-up period of five years in 872 patients who underwent resection as a part of a prospective observational study in carcinoma of the proximal and distal parts of the stomach. Surgeons believe that, in the median, only one-fifth of the patients with and without systematic lymphadenectomy had positive nodes, whereas pathologists found almost three-fourths of positive lymph nodes (72.7 percent) in patients with proximal carcinoma of the stomach as compared with those without systematic lymphadenectomy (30.8 percent). The figures for middle and lower third carcinomas were even higher (63.5 versus 13.9 percent and 75.9 versus 27.1 percent). Positive nodes were most common in the perigastric area and their distribution was clearly related to the site of the tumor. Frequently, however, lymph node groups were involved, far from the primary, that is, along the hepatoduodenal ligament in 9 to 19 percent of patients with carcinoma of the proximal part of the stomach and in 7 to 16 percent of patients with carcinoma of the distal part of the stomach. There were some hints of a better survival rate for patients with systematic lymphadenectomy as compared with those without, only for low stage carcinoma of the stomach (TNM stage IA-IB, p = 0.1157, Breslow). We suggest a more extensive operation with gastric resection, always combined with systematic lymphadenectomy if no distant metastases are found.

Adenocarcinoma↗

[Color-coded duplex sonography in the diagnosis of renal venous thromboses in the early phase following kidney transplantation].

A total of 91 colour-coded duplex Doppler ultrasound scans were performed in the early phase following renal transplantation in 53 out of 109 patients (48.6%) between 1. 1. 1992 and 15. 3. 1993. The indications for the investigation were primary failure of functional improvement in the transplanted kidney or secondary worsening of function. In five of the 53 patients (ten scans) constant retrograde flow in the segmentary arteries provided specific evidence of renal vein thrombosis, this diagnosis being confirmed histologically following nephrectomy. The Pourcelot index was raised (RI > 0.72) in all five cases. The RI was also raised in 35 of 53 patients; however, continuous retrograde diastolic flow was absent. The results of renal biopsy and the clinical course both excluded renal vein thrombosis in these cases. The colour Doppler ultrasound scans were unremarkable in 13 patients. The comparison group consisted of 151 patients in the later posttransplantation phase (> 2 months), in whom 171 colour Doppler ultrasound scans showed no signals associated with renal vein thrombosis. In agreement with the literature, these results show that colour-coded duplex Doppler ultrasound should be regarded as the definitive diagnostic procedure for renal vein thrombosis after transplantation, and if positive findings are obtained further invasive diagnostic procedures can be avoided.

Adolescent↗