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Biomedical subjects

R Lange

Publications and source records attributed to R Lange.

At least 145 records · Page 8Linked to original sources

Does pelvic magnetic resonance imaging differentiate among the histologic subtypes of uterine leiomyomata?

OBJECTIVE: To evaluate if pelvic magnetic resonance imaging (MRI) is reliable for differentiating leiomyoma subtypes. DESIGN: Prospective study. SETTING: Academic center. PATIENT(S): Forty-five patients underwent MRI before surgery for leiomyomata. INTERVENTION(S): One radiologist blinded to patient history and histologic diagnosis recorded the MRI characteristics and classification of the largest leiomyoma. MAIN OUTCOME MEASURE(S): Comparison of MRI and histologic diagnoses. RESULT(S): Leiomyoma subtypes were diagnosed accurately by MRI in 69% of cases. Magnetic resonance imaging had a 95% sensitivity and 72% specificity for diagnosing an uncomplicated leiomyoma and a 10% sensitivity and 100% specificity for a cellular leiomyoma. For cystic leiomyomata, the sensitivity was 80% and specificity was 98%, and for hemorrhagic leiomyomata, 100% and 86%, respectively. Magnetic resonance imaging correctly diagnosed all malignant tumors and did not incorrectly diagnose a leiomyoma as a leiomyosarcoma in any case. Ill-defined MRI margins were significantly more likely to be leiomyosarcoma, whereas well-defined margins were characteristic of benign lesions. Hemorrhagic leiomyomata were significantly more likely to be hyperintense on T1-weighted images than other subtypes. CONCLUSION(S): Although MRI is only fairly accurate in differentiating the subtypes of benign uterine smooth muscle tumors, signal intensities and margin characteristics are useful to distinguish accurately benign from malignant tumors.

Adult↗

Psychological distress in patients awaiting heart transplantation.

Heart transplantation has become an established procedure for the treatment of terminal heart failure. However, due to a shortage of donor organs, the waiting period for a donor organ is increasing. Cross-sectional and retrospective studies have indicated that there is tremendous psychological distress during this waiting period. The aim of this study was to assess this phase systematically and longitudinally. At the beginning of their waiting period, 62 patients at the Heidelberg Transplantation Centre were examined with regard to their physical complaints, quality of life, and level of depression. Four months later the remaining 42 patients were re-examined. The sample showed a significant increase (p<0.001) in subjective physical symptoms and an impairment in social activities (p<0.05) and everyday life (p<0.05), and a significant increase in depression (p<0.001), despite the relatively short time period. These results show the necessity of supportive psychotherapy for patients undergoing heart transplantation.

Adult↗

Tyrosine and serine phosphorylation of the neural cell adhesion molecule L1 is implicated in its oligomannosidic glycan dependent association with NCAM and neurite outgrowth.

We have previously shown that a cis interaction between the cell adhesion molecules L1 and NCAM is mediated by N-linked oligomannosidic glycans carried by L1 and that this L1/NCAM association is involved in basal neurite outgrowth from early postnatal cerebellar neurons of mouse brain [R. Horstkorte et al., J. Cell Biol. 121, 1409-1421 (1993)]. Extending these earlier studies we investigated signal transduction mechanisms elicited by this molecular interaction. We show here that phosphorylation of L1 is reduced concomitant with reduced neurite outgrowth when the L1/NCAM interaction is inhibited by oligomannosidic glycopeptides. Similarly, when a peptide of the 4th immunoglobulin (Ig)-like domain of NCAM - representing part of NCAM's carbohydrate-binding site - was added to the culture medium of the cells, neurite outgrowth and phosphorylation of L1 was strongly reduced. No effect on neurite outgrowth and phosphorylation of L1 was observed when cells were maintained in the presence of a peptide comprising part of the 1st Ig-like domain of NCAM or in the presence of the peptide encoded by the variable alternative spliced exon (VASE), which is also located in the 4th Ig-like domain of NCAM. Furthermore, phosphorylation of tyrosine and serine residues of L1 is reduced when the L1/NCAM interaction at the cell surface of cerebellar neurons is perturbed. Our observations suggest that a signal transduction mechanism is implicated in basal neurite outgrowth in which both tyrosine and serine phosphorylation of L1 represent a possible proximal step. Some of these results were presented at the International Glycoconjugate Symposium in Seattle, USA [P. C. Heiland et al., Glycoconj. J. 12, 521(1995)].

Amino Acid Sequence↗

Lack of evidence for an association between TTV infection and severe liver disease.

BACKGROUND: In 1997 a new human virus, TTV, was identified. The clinical significance of the TTV infection, however, remains unknown. OBJECTIVE: Establishment of the prevalence of TTV DNA in different population groups in Germany and the assessment of the possible clinical significance of TTV infection. STUDY DESIGN: Detection of the TTV DNA by PCR in blood donors, patients with end-stage liver disease, and multiple transfused patients with haemotological disorders. RESULTS: TTV DNA was detected in 16 of 122 (13.1%) volunteer blood donors, in 34 of 77 (44.2%) patients with end-stage liver disease, and in 21 of 38 (55.3%) multiple transfused patients. There was no difference in the prevalence of the TTV DNA in end-stage liver disease patients with regard to sex, age, presence of HCV and HBV infection markers, and etiology of liver disease. Phylogenetic analysis of the amplified DNA fragments from 12 randomly selected TTV infected subjects demonstrated that in Germany at least two putative TTV genotypes and four subtypes are circulating. CONCLUSIONS: (i) TTV is widely spread in German population; (ii) one of the possible ways of its transmission is blood transfusion; (iii) TTV infection most probably does not generally lead to the development of the end-stage liver disease.

Adult↗

Influence of different fat emulsion-based intravenous formulations on the pharmacokinetics and pharmacodynamics of propofol.

PURPOSE: The influence of different intravenous formulations on the pharmacokinetics and pharmacodynamics of propofol was investigated using the effect on the EEG (11.5-30 Hz) as pharmacodynamic endpoint. METHODS: Propofol was administered as an intravenous bolus infusion (30 mg/kg in 5 min) or as a continuous infusion (150 mg/kg in 5 hours) in chronically instrumented male rats. Propofol was formulated as a 1% emulsion in an Intralipid 10%-like fat emulsion (Diprivan-10, D) or as a 1%- or 6% emulsion in Lipofundin MCT/LCT-10% (P1% and P6%, respectively). EEG was recorded continuously and arterial blood samples were collected serially for the determination of propofol concentrations using HPLC. RESULTS: Following bolus infusion, the pharmacokinetics of the various propofol emulsions could adequately be described by a two-compartmental pharmacokinetic model. The average values for clearance (Cl), volume of distribution at steady-state (Vd,ss) and terminal half-life (t1/2, lambda 2) were 107 +/- 4 ml/min/kg, 1.38 +/- 0.06 l/kg and 16 +/- 1 min, respectively (mean +/- S.E. n = 22). No significant differences were observed between the three propofol formulations. After continuous infusion these values were 112 +/- 11 ml/min/kg, 5.19 +/- 0.41 l/kg and 45 +/- 3 min, respectively (mean +/- S.E., n = 20) with again no statistically significant differences between the three propofol formulations. Comparison between the bolus- and the continuous infusion revealed a statistically significant difference for both Vd,ss and t1/2, lambda 2 (p < 0.05), whereas Cl remained unchanged. In all treatment groups infusion of propofol resulted in a burst-suppression type of EEG. A profound hysteresis loop was observed between blood concentrations and EEG effect for all formulations. The hysteresis was minimized by a semi-parametric method and resulted in a biphasic concentration-effect relationship of propofol that was described non-parametrically. For P6% a larger rate constant onset of drug effect (t1/2,keo) was observed compared to the other propofol formulations (p < 0.05). CONCLUSIONS: The pharmacokinetics and pharmacodynamics of propofol are not affected by to a large extent the type of emulsion nor by the concentration of propofol in the intravenous formulation.

Anesthetics, Intravenous↗

Interplay between global regulators of Escherichia coli: effect of RpoS, Lrp and H-NS on transcription of the gene osmC.

The transcription of the osmC gene of Escherichia coli is regulated as a function of the phase of growth. It is induced during the decelerating phase, before entry into stationary phase. osmC expression is directed by two overlapping promoters, osmCp1 and osmCp2. osmCp2 is mainly transcribed by E-sigma(s), the RNA polymerase using the sigma(s) (RpoS) sigma factor, and is responsible for the growth phase regulation. Transcription from osmCp1 is independent of sigma(s). The leucine-responsive protein (Lrp) has been shown to bind the osmC promoter region in band shift experiments. In vivo analysis using osmC-lacZ transcriptional fusions demonstrated that Lrp affects the expression of both promoters. It represses the transcription of osmCp1 and activates the transcription of osmCp2 by E-sigma(s). An absence of Lrp results in an increase in the amount of RpoS during exponential growth in minimal medium. The nucleoid-associated protein H-NS also represses osmC transcription from both promoters. However, this happens through different mechanisms. The effect on osmCp2 is probably mediated by the increase in sigma(s) concentration in the cytoplasm of hns- mutants, while the effect on osmCp1 is independent of sigma(s). No binding of H-NS to the promoter region DNA could be detected, indicating that the effect on osmCp1 could also be indirect.

Artificial Gene Fusion↗

Ketoprofen (25 mg) in the symptomatic treatment of episodic tension-type headache: double-blind placebo-controlled comparison with acetaminophen (1000 mg).

Therapies in current use for episodic tension-type headache (ETTH) are often unsatisfactory. Few trials have been conducted to demonstrate efficacy of any of them. This multicenter placebo-controlled randomized parallel-groups study compared the analgesic efficacy of single oral doses of ketoprofen 25 mg and acetaminophen 1000 mg as outpatient treatment of 1 attack of ETTH. Efficacy was assessed by patients as pain relief on a diary-entered 7-point categorical scale. A total of 457 patients treated 348 attacks, 330 of which were evaluable. There were no serious adverse events (AEs); gastrointestinal AEs were most common on all treatments. Total relief from pain after 2 h was recorded by 16% of patients on placebo, 28% on ketoprofen, and 22% on acetaminophen. Worthwhile effect or total relief (all other responses were regarded as treatment failures) were recorded by 36% on placebo, 70% on ketoprofen (p < 0.001), 61% on acetaminophen (p < 0.001). The difference between ketoprofen and acetaminophen was not significant (p = 0.24). Various secondary efficacy measures confirmed superiority of both active treatments over placebo, with some trends for slightly better outcome on ketoprofen that on acetaminophen. This study demonstrates that ketoprofen is an effective alternative to standard therapy in ETTH.

Acetaminophen↗

Increased frequency of congenital chromosomal aberrations in female partners of couples undergoing intracytoplasmic sperm injection.

We evaluated the frequency of congenital chromosomal aberrations in a sample of 305 couples included in an intracytoplasmic sperm injection (ICSI) programme. Twenty individuals (3.3%) with congenital chromosomal abnormalities could be identified. The following types of abnormalities were observed: reciprocal translocations (n = 7), Robertsonian translocations (n = 3), inversions (n = 3), other structural aberrations (n = 4) and sex chromosome aberrations (n = 3). The rate of chromosomally abnormal males (10/305, 3.3%) lay within the expected range for patients with reduced semen quality. Surprisingly, 50% (10/20) of all abnormal karyotypes were contributed by the female partner of ICSI patients. These data confirm the higher incidence of chromosomal aberrations in infertile populations as compared with the baseline population risk. Additionally, the data imply that in some cases of male factor infertility a hidden female chromosomal factor may be present, which cannot be identified by standard clinical evaluation. In conclusion, we recommend chromosomal analysis in both partners of couples undergoing ICSI treatment.

Adult↗

In vivo adulteration: excess fluid ingestion causes false-negative marijuana and cocaine urine test results.

Drug users can be highly motivated to obtain negative results on urine drug tests and may attempt to subvert the process by in vivo adulteration. The use of herbal products for "flushing" and "detoxification" is frequently advertised as an effective means of passing drug tests. Accordingly, a study was designed to determine the effects of ingestion of two herbal products, Naturally Klean Herbal Tea and Golden Seal root, and a diuretic medication, hydrochlorothiazide. The herbal tea was prepared in 1 gal of water as specified by the manufacturer. All other products were consumed with 1 gal of water. Two control conditions in which the subject consumed only water (1 gal; 12 oz) were included. The 1-gal liquid treatments were divided into 4-qt aliquots, and 1-qt was consumed each hour for 4 h. All treatments were begun approximately 22 h after smoking of a marijuana cigarette (3.58% THC) and 22 h after intranasal administration of cocaine hydrochloride. Following all treatments with excess fluid, creatinine and specific gravity dropped in 1.5-2.0 h to levels indicative of diluted specimens (<20 mg/dL creatinine, <1.003 specific gravity). Marijuana and cocaine metabolite concentrations by immunoassay (EMIT and TDx) also dropped rapidly, and the results frequently switched from positive to negative. By the time subjects had consumed 2 qt of any fluid, they were generally producing false-negative results. For example, ingestion of excess water produced dilute specimens (<20 mg/dL creatinine; <1.003 specific gravity) in an average time plus or minus the standard error of the mean of 1.47 +/- 0.17 h (N = 5) and 1.45 +/- 0.2 h (N = 5) following smoked marijuana and intranasal cocaine, respectively. In comparison, ingestion of Klean Tea produced dilute specimens in 1.36 +/- 0.07 h (N = 4) and 1.39 +/- 0.11 h (N = 4) following marijuana and cocaine administration. Recovery of urine test measures to pre-treatment levels occurred over a period of 8-10 h. Average detection times for marijuana metabolite appeared to be slightly shorter following ingestion of 1 gal of fluids compared with ingestion of 12 oz of water as a result of the time of testing being near the end of the cannabinoid metabolite excretion phase. Consequently, negative cannabinoid results induced by fluid ingestion rarely returned to positive after excess water was eliminated. In contrast, negative cocaine results reverted to positive quickly after the dilution effects disappeared. It was concluded that excess water ingestion can produce false-negative test results, but the claims of herbal products to be an aid in passing a urine test appear to be unfounded.

Adult↗

Delusions of the paranormal: a haunting question of perception.

The hypothesis that paranormal (poltergeist) experiences are delusions resulting from the affective and cognitive dynamics of percipients' interpretation of ambiguous stimuli was tested in two studies using a structural modeling approach. Consistent with attribution theory, study I indicated that such delusions are best modeled by a closed negative-feedback loop involving belief, experience, and fear as process variables. Using a more homogeneous sample of percipients, study II replicated this model and the relations among the process variables reached statistical significance. The findings extend established attributional models of delusions by incorporating psychosocial and cognitive factors, including age, gender, and tolerance of ambiguity. The model is proposed as a general framework for the understanding and study of delusions and contagious psychogenic illness, in particular.

Adolescent↗

Computed tomography in the initial evaluation of hemodynamically stable patients with blunt abdominal trauma: impact of severity of injury scale and technical factors on efficacy.

BACKGROUND: Although computed tomography is used widely in evaluating injuries from blunt abdominal trauma, grading of injuries does not reliably predict the need for intervention. Objective reporting is essential to evaluate accuracy and facilitate patient triage. We established and tested a five-point grading system for overall severity of injury. METHODS: A total of 392 computed tomographic trauma cases were objectively classified according to the type and severity of abdominal injuries, by two experienced radiologists. Interobserver variability between the original interpretation and the consensus of the film reviewers was evaluated. The computed tomographic grading system was measured against rate of admission, exploratory laparotomy, and further imaging. RESULTS: Patients with higher grades of injury on computed tomography were increasingly likely to have surgical management (odds ratio, 3.99; 95% confidence interval, 1.86-8.58; p < 0.0006), with sensitivity 100%, specificity 89.5% for level 2 injuries and higher. Although there was almost perfect agreement between the official interpretation and the reviewers' blinded consensus interpretation (raw agreement 84%, weighted kappa 0.86), indeterminate studies were reduced from 23% (16 of 67) to 12% (8 of 67) on review: these were more likely to have metallic or motion artifacts (5 of 16 vs. 1 of 51 p < 0.002). CONCLUSIONS: Standardizing reporting of injuries enhances accuracy, and grading eliminates equivocation. Diagnostic certainty in computed tomography of blunt abdominal trauma is reduced by motion and metallic artifacts.

Abdominal Injuries↗

Modeling precognitive dreams as meaningful coincidences.

50 college students completed the Anomalous Experiences Inventory, the AT-20 measure of tolerance of ambiguity, and a frequency of dream recall questionnaire. Using path analysis we show that precognitive dreams can be modeled as accidental 'hits' with increased dream recall and the interpretation of such hits as 'meaningful coincidences' seems facilitated by a belief in the paranormal. As predicted, both factors are affected by tolerance of ambiguity, which provides the flexibility required to store and recall ambiguous dream information while simultaneously allowing dream recallers to assume a paranormal origin of their 'precognitive' dreams. Moreover, the fit of the proposed model did not depend on sex or age. Alternative models that provided a better fit to the data validated the roles of tolerance of ambiguity and belief in the paranormal in eliciting experiences of precognitive dreaming, but frequency of dream recall was not confirmed as a crucial factor.

Adolescent↗

Comparison of single- and triple-dose contrast material in the MR screening of brain metastases.

PURPOSE: Although studies obtained with triple-dose contrast administration can show more brain metastases than those obtained with single-dose contrast material in patients with multiple metastases, such studies are costly and of limited clinical benefit. Since most patients who undergo screening have negative findings or a single metastasis, this study was performed to compare the clinical utility of single-dose versus triple-dose contrast administration in this large group of patients who could benefit from the possible increased sensitivity in lesion detection. METHODS: Ninety-two consecutive patients with negative or equivocal findings or a solitary metastasis on single-dose contrast-enhanced MR images underwent triple-dose studies. Findings were compared with a standard of reference composed of panel review and long-term follow-up. Further analysis was performed by comparing results with those obtained by two blinded readers. RESULTS: In all 70 negative single-dose studies, the triple-dose studies depicted no additional metastases in terms of the standard of reference. No statistically significant difference was seen between the results of the single- and triple-dose studies. For 10 equivocal single-dose studies, the triple-dose study helped clarify the presence or absence of metastases in 50% of the cases. In 12 patients with a solitary metastasis seen on the single-dose study, the triple-dose study depicted additional metastases in 25% of the cases. In the results of one of the two blinded readers, use of triple-dose contrast led to a statistical difference by decreasing the number of equivocal readings but at the expense of increasing the number of false-positive readings. CONCLUSION: Routine triple-dose contrast administration in all cases of suspected brain metastasis is not helpful. On the basis of our investigation, we conclude that the use of triple-dose contrast material is beneficial in selected cases with equivocal findings or solitary metastasis, although with the disadvantage of increasing the number of false-positive results.

Brain↗

Liver transplantation in a 29-year-old patient with gallbladder carcinoma complicating primary sclerosing cholangitis.

Patients with primary sclerosing cholangitis (PSC) are at increased risk for cholangiocarcinoma. This tumor usually is a fatal complication, median survival after diagnosis is less than six months. In an asymptomatic 29-year-old patient with long-standing PSC and ulcerative colitis, routine abdominal ultrasound demonstrated an irregular mass, 11 x 13 mm, in the gallbladder. Cholecystectomy was performed, and histological examination demonstrated a moderately differentiated adenocarcinoma with infiltration of all layers of the gallbladder and invasion of local lymphatic vessels. Extensive diagnostic work-up failed to consistently demonstrate metastatic disease, and the patient was offered a liver transplantation. 24 months after the operation, the patient feels well and there is no indication of tumor recurrence. In carefully selected patients with gallbladder carcinoma complicating PSC, liver transplantation may be a therapeutic option.

Adenocarcinoma↗

[Carcinoid syndrome. Recurrent upper abdominal pain, diarrhea and flush in a 15-year-old girl].

BACKGROUND: A carcinoid syndrome is typically diagnosed in elderly patients, median age at diagnosis was 60 years in two large series. We describe a patient with the carcinoid syndrome at the young age of 15 years. CASE REPORT: The 15-year-old patient's history and findings on physical examination, clinical chemistry, abdominal ultrasound and liver biopsy were typical for a carcinoid with hepatic metastases. The patient's age, however, was very unusual. Because of her youth, we discussed a potentially curative treatment with resection of the primary tumor in the upper jejunum followed by liver transplantation at a second operation. This concept had to be abandoned, when the first operation revealed a tumor in the mesenterium, close to the primary, 5 cm in diameter and around the superior mesenteric artery. This tumor could not be resected. Liver transplantation therefore did not offer this young patient a chance for cure.

Abdominal Pain↗

A central role for water in the control of the spin state of cytochrome P-450scc.

A previous thermodynamic study [Lange, R., Larroque, C. & Anzenbacher, P. (1992) Eur. J. Biochem. 207, 69-73] demonstrated two conformations (A and B) of cytochrome P-450scc (SCC), the enzyme which initiates steroid biosynthesis by cleaving the side chain of cholesterol. The conformation found at the lowest temperatures (form A) displays a six-ligand high-spin heme iron [Hildebrandt, P., Heibel, G., Anzenbacher, P., Lange, R., Krüger, V. & Stier, A. (1994) Biochemistry 33, 12920-12929]. Analytical centrifugation shows that the oligomeric composition of SCC is the same for the A and the B conformers. However, as revealed by fourth-derivative ultraviolet spectroscopy, the two conformers differ in the mean environment of the tryptophan residues, which was more polar in the A form. The structural role of water in these two conformations was investigated using the pressure-jump technique under various pH, temperature and osmotic-stress conditions. Applying hydrostatic pressure to SCC induced very slow (tau >30 min) biexponential relaxation kinetics corresponding to the high-spin to low-spin transition. Analysis of the activation volumes suggested a dissociative mechanism for the A conformer (+45 ml/mol), and an associative mechanism for the B conformer (-39 ml/mol). Applying osmotic stress to the A form changed its kinetic characteristics to those of the B form. These results are consistent with a model comprising a solvent intake (ten water molecules) between the B and the A conformers and protonation of their respective high-spin states. The sixth ligand of the high-spin form in the A conformer involves a water molecule and an unknown constraining structure.

Centrifugation↗