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Biomedical subjects

A Wolf

Publications and source records attributed to A Wolf.

At least 199 records · Page 11Linked to original sources

[Diagnostic value of continuous wave (cw) Doppler sonography in maternal diabetes mellitus].

Doppler studies of umbilical, uterine and arcuate artery velocity wave forms were performed in 40 insulin-dependent diabetic women in the first and second half of pregnancy. Using a continuous-wave Doppler device, the resistance index (RI) was calculated to determine the degree of vascular resistance in utero-placental and foeto-placental compartment. The 90th percentile was used to classify flow velocity profiles. In addition, diastolic notching and incomplete registration of uterine and arcuate arteries were considered as an abnormal result in utero-placental perfusion. The prevalence of abnormal velocity wave forms in this risk group was higher than in a non-diabetic population. No significant correlation was found between abnormal Doppler studies and White's classification. Patients with vasculopathy represent a high-risk group for foetal growth retardation, which may be detected early by umbilical and especially uterine artery Doppler studies. Abnormal uterine and arcuate artery wave forms allowed identification of patients who developed pregnancy-induced hypertension/preeclampsia.

Asphyxia Neonatorum↗

Polynomial analysis of placental flow patterns in growth-retarded fetuses.

Correct interpretation of conspicuous blood flow velocity waveforms cannot rely solely on the evaluation of uteroplacental vascular Doppler flow patterns by means of angle-independent indices such as the resistance or pulsatility index. In addition to the degree of pulsatility, the waveform shape between the systolic and diastolic peak values is of considerable consequence. A subdivision of the total flow waveform into orthogonal polynomial components allows both pulsatility evaluation and notching to be registered, providing a higher sensitivity in identification of pathological vascular resistance. Accurate recording and assessment of the flow waveform is therefore an important qualitative criterion for the classification of Doppler flow patterns in pregnancies with reduced uteroplacental perfusion.

Blood Flow Velocity↗

Improving the outcome of severe head injury with the oxygen radical scavenger polyethylene glycol-conjugated superoxide dismutase: a phase II trial.

Formation of the oxygen radical superoxide anion is one of the final events of several metabolic pathways in the cascade that leads to delayed neuronal death after traumatic or ischemic brain injury. In the laboratory, scavenging of the superoxide anion with native superoxide dismutase (SOD) or polyethylene glycol (PEG)-conjugated SOD (PEG-SOD) has been shown to be beneficial in several types of traumatic and ischemic injury. Accordingly, PEG-SOD was utilized in a randomized controlled Phase II trial to evaluate its safety and efficacy in severely head-injured patients with a Glasgow Coma Scale score of 8 or less. At two institutions, 104 patients were randomly assigned to receive either placebo or PEG-SOD (2000, 5000, or 10,000 U/kg) intravenously as a bolus, an average of 4 hours after injury. Prognostic factors were evenly distributed in the four groups, except for mean age which was significantly higher in the group receiving 10,000 U/kg than in the placebo group (mean age 34 years vs. 25 years). No complications attributed to the study medication were noted. The average intracranial pressure (ICP) was similar in the four groups, but the percentage of time during which ICP was above 20 mm Hg was less in the groups receiving 5000 or 10,000 U/kg of PEG-SOD. Patients in the group receiving 10,000 U/kg also required less mannitol for ICP control than the placebo group. Outcome was assessed using the Glasgow Outcome Scale at 3 and 6 months postinjury in 91 and 93 patients, respectively, by blinded observers not involved in the clinical management of the patients. At 3 months, 44% of patients in the placebo group were vegetative or had died, while only 20% of patients in the group receiving 10,000 U/kg of PEG-SOD were in these outcome categories (p < 0.03, multiple logistic regression test); at 6 months, these figures were 36% and 21%, respectively (p = 0.04). Differences in outcome between the placebo group and either of the other two dosage groups were not statistically significant. It is concluded that PEG-SOD was generally well tolerated and appears promising in improving outcome after severe head injury. A larger, multicenter, Phase III trial, using a higher dose (20,000 U/kg) compared to placebo and to 10,000 U/kg of PEG-SOD is planned.

Adult↗

Efficacy and tolerability of galactosamino-glycuronoglycan-sulfate in osteoarthritis of the knee: an 11-month experience.

Chondroprotective agents represent a model for basic therapy of osteoarthritis (OA), thanks to their activity directed towards the protection and repair of articular cartilage. One of the most recent compounds capable of interfering with the pathogenic mechanisms of OA is galactosamino-glycuronoglycan-sulfate (GGGS), a highly depolymerized glycosaminoglycan with favourable chondroprotective and anti-inflammatory properties. The present paper describes the experience with GGGS given to a group of patients with symptomatic OA of the knee as compared to a parallel group treated with placebo. The drug (or placebo) was administered in two series of 25 intramuscular injections each over a period of 11 months, and four successive evaluations of treatment were made at various times during this period, and a fifth evaluation one month after the suspension of treatment to better evaluate the permanence of the therapeutic effect. The results obtained showed significant improvements on pain, algofunctional index and consumption of NSAIDs only in the group treated with GGGS. The drug was well tolerated and no reduction of dosage or drop-out from therapy were required. The favourable clinical effects and the patients' good compliance make GGGS a useful drug for successful chondroprotective treatment of OA.

Aged↗

Hemodynamic parameters in patients with acute cervical cord trauma: description, intervention, and prediction of outcome.

The cardiovascular response of the patient with acute spinal cord injury (SCI) is known to be altered secondary to the cord injury. Our current protocol of managing the acute phase of patients with SCI includes invasive hemodynamic monitoring (with arterial line and Swan-Ganz catheter) and support with fluids and dopamine and/or dobutamine, titrated to maintain a hemodynamic profile with adequate cardiac output (to be determined by oxygen consumption and delivery) and a mean blood pressure of > 90 mm Hg. We feel that this protocol provides two benefits: 1) maintaining the mean blood pressure improves the morbidity of these patients by deterring ischemia and accompanying secondary insults; 2) aggressive monitoring and hemodynamic intervention help stabilize the hemodynamic status of these patients and make it possible to consider early surgery in selected cases. Our hypothesis is that the pulmonary vascular bed is more sensitive to the sympathectomized effect of acute complete cervical SCI. We analyzed the demographic, neurologic, and hemodynamic data of 50 consecutive patients during their first week postinjury. All had signs of myelopathy; 31 (62%) were considered clinically complete. Of the 50 patients, 9 (18%) died, 20 did not improve functionally, and 21 improved. The mean heart rate (82.1 +/- 13.3), blood pressure (94.4 +/- 9.4), pulmonary artery pressure (22 +/- 5) and wedge (12.7 +/- 3.4), cardiac index (4.5 +/- 0.9), systemic vascular resistance index (SVRI) (1637 +/- 399), pulmonary vascular resistance index (PVRI) (181 +/- 80), and oxygen transport (694 +/- 156) showed good response to the treatment. Because the measurements were obtained during treatment, they differ from the expected "classic sympathectomized" response, but they provide a database for further analysis of hemodynamic manipulation in SCI. An analysis of the hemodynamic parameters did not differentiate between complete and incomplete lesions or between patients with functional improvement. We determined, on the basis of the initial hemodynamic measurements, that no patient with a clinically complete motor deficit (Frankel Grade A+B) improved of the 10 who had measurements compatible with either: 1) PVRI < 100 with SVRI < 1200; or 2) PVRI < 115 with SVRI < 1300 or PVR/SVR ratio of < 0.08 when SVRI was < 1600. These patients could not have other measurements that showed low SVRI < 1350 with PVRI > 139. At odds with this unique group, 13 of 29 patients with the same clinical picture and without the above physiological criteria of severe hemodynamic deficit eventually improved (P < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

Oxygen free radical production mediated by cocaine and its ethanol-derived metabolite, cocaethylene, in rat hepatocytes.

Cocaine ethyl ester ("cocaethylene") is a cocaine metabolite formed by hepatic carboxylesterases in the presence of ethanol. In the human liver, this pharmacologically active cocaine analog may reach concentrations similar to those of cocaine. To further investigate the intrinsic hepatotoxic potential of cocaethylene and to compare its effects with the known hepatocyte-damaging effects of cocaine, primary short-term cultures of hepatocytes derived from phenobarbital-pretreated rats were exposed to cocaine or cocaethylene (10 to 1000 mumol/L). Both drugs caused time- and concentration-dependent release of lactate dehydrogenase into the extracellular medium in a congruent pattern. Spontaneous hydrolysis of cocaethylene was negligible at pH 7.4, and the rate of 2-diethylaminoethyl-2,2-diphenylvalerate (SKF-525A) and phenylmethylsulfonylfluoride-sensitive enzymatic degradation in hepatocyte cultures was similar to that of cocaine (half-time, approximately 3 hr). Furthermore, both cocaine and cocaethylene induced massive NADPH-dependent reactive oxygen species production in hepatic microsomal suspensions and in homogenates of cultured hepatocytes, as directly demonstrated by superoxide dismutase- and catalase-sensitive luminol chemiluminescence. The integrated photon emission and the maximal slopes of the luminol chemiluminescence displayed similar concentration-response curves for cocaine and cocaethylene. These data suggest that reactive oxygen species, generated during the interaction of cocaine and cocaethylene with cytochrome P-450, may be the common mediators of hepatotoxicity induced by these compounds. Moreover, they indicate that the potential for cocaethylene to induce acute lethal cell injury in hepatocytes through oxidative mechanisms is similar to that of its parent compound, cocaine.

Animals↗

[Laparoscopy in clinical practice. I. Indications].

In the paper the authors analyzed indications to 1527 laparoscopies. The most frequent indications were: sterility (72.2%) and suspicions of adnexal tumours or extrauterine gravidity (14.1%). In 173 diagnostically difficult cases laparotomy was avoided. In these cases laparoscopy allowed to exclude the pelvic pathology or to quality to laparoscopic operation of ovarian cysts and intact tubal pregnancy. Diagnostic and operative laparoscopy give the possibility of quick diagnosis in diagnostically difficult cases and enables avoidance of laparotomy in many cases.

Adolescent↗

[Laparoscopy in clinical practice. II. Usefulness in diagnosis of sterility].

The paper presents results of 1099 laparoscopies performed in sterility. Laparoscopy was made in the second phase of the menstrual cycle, 5 to 7 days after probable ovulation, as a last stage in diagnosis of sterility. Normal state of genital organs and minor pelvis was noted in 20.9% of investigated patients. In the remaining more than one etiologic factor was found, which may influence the sterility. The authors concluded, laparoscopy is valuable, accessory method in the diagnosis of sterility, which enables sometimes to find the etiologic factor in patients with "unexplained infertility".

Adult↗

[Laparoscopy in clinical practice. III. Complications].

In the paper authors made analysis of complications, which have appeared among 1527 laparoscopies. The authors noted complications in 14 cases (0.91%) among the whole laparoscopic interventions. The most frequent complication was subcutaneous oedema, which was noted in 7 cases (0.46%). Injury of internal organs was noted in 6 cases (0.39%) and cardiac arrest in 1 case (0.06%). In author's opinion laparoscopy carry a small risk of complications.

Edema↗

[The value of continuous wave Doppler ultrasound in risk pregnancy-intrauterine growth retardation and pregnancy-induced hypertension].

To evaluate the frequency of abnormal doppler results in pregnancies complicated by placental insufficiency, flow waveforms of 100 patients with documented intrauterine growth retardation--birthweight below the 10th percentile--were analysed. Uterine, arcuate and umbilical artery velocimetry were performed by means of a continuous wave Doppler ultrasound. Neither the range of serial examination nor the interval between last prepartal doppler test und delivery showed influence on the doppler results. Compared to normal pregnancy, a significant increase of diastolic notching and incomplete registration of maternal vessels were found. Using 90th percentile as cut-off limit last doppler examination before delivery showed pathological results in 76% of all cases with growth retardation and 90% of pregnancies with an additional risk of pregnancy induced hypertension. As pathological waveforms in the maternal compartment contribute a major part to abnormal velocity waveforms, doppler study of utero-placental vessels plays an important role in the diagnose of impaired persuasion of the placenta.

Blood Flow Velocity↗

Nonrandom distribution of gp120 N-linked glycosylation sites important for infectivity of human immunodeficiency virus type 1.

More than 20 consensus N-linked glycosylation sites occur in the gp120 coding sequence of most isolates of human immunodeficiency virus type 1. Based on the N-linked glycosylation pattern of a well-characterized recombinant gp120, it is likely that N-linked sugars are present at most, if not all, of the consensus glycosylation sites of the heavily glycosylated gp120. In this study, we evaluated the relative importance of each of the 24 N-linked glycosylation sites of gp120 in the molecular clone HXB2 to viral infectivity. The ability of HXB2-derived mutants, each having 1 of the 24 N-linked glycosylation sites mutated by site-directed mutagenesis, to infect CD4-positive SupT1 cells was compared with that of the wild-type virus. We found that most of the individual consensus N-linked glycosylation sites are dispensable for viral infectivity. The five consensus N-linked glycosylation sites that are likely to have important roles in infectivity are all located in the amino-terminal half of gp120, indicating that the N-linked glycosylation sites that are important for infectivity of human immunodeficiency virus type 1 are not randomly distributed in gp120. We predict that a partially glycosylated gp120 with most of the dispensable N-linked glycosylation sites removed may be a better vaccine candidate than the fully glycosylated gp120.

Amino Acid Sequence↗

The spectrum of CFTR mutations in south-west German cystic fibrosis patients.

The cystic fibrosis transmembrane conductance regulator (CFTR) gene of 110 cystic fibrosis (CF) patients from the south-west of Germany was screened for 12 different mutations. This analysis resulted in an identification of 79% of all CF mutations and a complete genotype in 66% of the families. The most common mutation found was delta F508 (67%). Another 5 mutations accounted for a further 12.5% (4% G542X; 3% R553X; 3% N1303K; 2% 1717-1 G-->A; 0.5% G551D) whereas 6 mutations (R117H, A455E, delta I507, S549I, S549N, and R1162X) were not found. Fifty-four (49%) patients were delta F508 homozygotes and 18 (16.5%) were compound heterozygotes for delta F508 and one of the rarer mutations. These frequencies differ slightly from those found in the north of Germany and considerably from those reported from the south of Europe, which seems to be consistent with a north to south decline of the relative abundance of delta F508. Two patients, age 6 and 25 years, were compound heterozygotes for G542X and N1303K. The clinical features of the 6 year old were characterised by severe gastrointestinal and as yet only mild pulmonary complications whereas the 25 year old manifested severe pulmonary and gastrointestinal symptoms indicating that the N1303K mutation of the C-terminal CFTR nucleotide binding fold significantly impairs protein function in both the pancreas and the lungs.

Adolescent↗

Reversal of multidrug resistance by B859-35, a metabolite of B859-35, niguldipine, verapamil and nitrendipine.

It has been shown previously that verapamil and other calcium antagonists and calmodulin inhibitors can reverse multidrug resistance. We compared the potency of the dihydropyridine derivatives (4R)-3-[3-(4,4-diphenyl-1-piperadinyl)-propyl]-5-methyl-1,4-dihydr o-2,6- dimethyl-4-(3-nitrophenyl)-pyridine-3,5-dicarboxylate-hydrochloride (B859-35), a metabolite of B859-35, niguldipine and (R)-nitrendipine to that of (RS)-verapamil in reversing multidrug resistance. The accumulation of the fluorescent dye rhodamine 123, which is transported by the P-glycoprotein, was determined by a flow cytometer. Multidrug-resistant human HeLa KB-8-5 and Walker rat carcinoma cells were incubated in the presence and in absence of the drugs indicated above. We found that 0.1 microM B859-35 increases the accumulation of rhodamine 123 in multidrug-resistant KB-8-5 and Walker cells more effectively than 1 microM (RS)-verapamil. In sensitive KB-3-1 cells addition of the drugs had no significant influence on the accumulation of rhodamine 123. IN KB-8-5 cells, 10 nM Adriamycin caused a reduction of cell growth to 85% compared to untreated controls (= 100%). If 1 microM B859-35, B859-35 metabolite, niguldipine, verapamil or (R)-nitrendipine was added to 10 nM Adriamycin, growth reduction compared with untreated controls increased to 12%, 11%, 23%, 63%, and 82% respectively. The effect of 0.1 microM B859-35 was a reduction in proliferation to 38%, that of 0.1 microM verapamil to 72%. These data illustrate that B859-35, a compound with antitumor activity in several tumors, is at least ten times more potent than racemic verapamil in reversing multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗