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Biomedical subjects

A Rudolph

Publications and source records attributed to A Rudolph.

At least 37 records · Page 2Linked to original sources

Effect of liposome-encapsulated hemoglobin on triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein cholesterol measurements.

The present study investigated the effect of liposome-encapsulated hemoglobin (LEH), an experimental oxygen-carrying resuscitation fluid, on triglyceride, total cholesterol, and low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol measurements. In vivo, the intravenous infusion of LEH (5.6 mL/kg, n = 6) elevated serum triglycerides (+92% vs. baseline, P < .05), total cholesterol (+25% vs. baseline, P < .01), LDL cholesterol (+72% vs. baseline, P < .01) and had no effect on serum HDL cholesterol. In addition, LEH did not alter the elevation in serum triglycerides (+302% vs. baseline, P < .01) and LDL cholesterol (+86% vs. baseline, P < .01) induced by lipopolysaccharide (3.6 mg/kg, i.v., n = 6. Ex vivo, measurements of triglycerides and total cholesterol as well as LDL and HDL cholesterol in whole blood from naive rats were not changed by the addition of LEH (0-50%, n = 6). In vitro, the addition of a fixed concentration of LEH (50%, n = 6) to varying concentrations of cholesterol solution (0-50%), or vice versa, had no effect on cholesterol determination. It is therefore concluded that LEH only minimally affects serum levels of triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol and does not interfere with their measurement.

Animals↗

Sudden infant death and maternal cigarette smoking: results from the Lower Saxony Perinatal Working Group.

Maternal smoking has long been identified as a risk factor for sudden infant death (SID). However, only few studies analysed the biological plausibility of the relationship between maternal smoking and SID. In Lower Saxony (North Germany), detailed information concerning the perinatal period is routinely obtained for almost all infants born in this region. The perinatal data sets from 190 SID cases who had died between 1986 and 1990 and in whom a full autopsy had been performed were identified and compared to data sets from 5920 random controls, frequency matched to cases on year of birth. After adjusting for potential confounders (socio-economic status, birth weight, maternal age and nationality), smoking during pregnancy was still associated with a significantly increased risk of SID (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.7-4.5). There was a clear dose-effect relationship between the number of cigarettes smoked and the risk of SID: adjusted ORs were 2.6 (1.5-4.4) for 1-10 cigarettes/day, 2.8 (1.8-6.0) for 11-20 cigarettes/day, and 6.9 (1.9-25.5) for > 20 cigarettes/day. There also appeared to be an interaction between smoking during pregnancy and maternal anaemia: the risk of SID almost doubled if mothers not only smoked, but were also anaemic (haemoglobin < 100 g/l). These results support the concept that smoking during pregnancy has direct biological effects on the fetus which are associated with an increased risk of SID later in life. The exact mechanism(s) whereby smoking increases the risk of SID, however, remains to be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Iron-Deficiency↗

Arterial oxygen saturation in infants at risk of sudden death: influence of sleeping position.

To study the possible influence of sleeping position on arterial oxygen saturation, measured by pulse oximetry (SpO2), 7-h overnight recordings of breathing movements and ECG were performed in 43 infants (median age 2.4 months, range 0.2-11 months) at increased risk of sudden infant death syndrome (SIDS). Infants were randomly allocated to start sleeping either in their usual sleeping position or in the opposite position. After 3.5 h, all infants were gently turned over. Thus, each infant served as their own control. Recordings were analysed for sleep time, baseline SpO2 (only during regular breathing), and the number and duration of desaturations (a decrease in SpO2 to < or = 80%). In the prone position, a significantly higher proportion of time was spent asleep (median 79% versus 70%; p < 0.05). Median baseline SpO2 was 98.8% (91.7-100%) in the prone and 99.0% (92.0-100%) in the supine position (ns). A total of 191 desaturations were found in 29 recordings; 96 in the prone and 95 in the supine position (ns). One infant subsequently died of SIDS while sleeping in the prone position. He had a relatively high number of desaturations (n = 12) which all occurred in the prone position. These results confirm earlier studies which could not find a significant influence of sleeping position on baseline oxygenation. The occurrence of desaturations in the prone position only in the infant who subsequently died requires further investigation.

Electrocardiography↗

Ultrastructural co-localization of neuropeptide Y and vasoactive intestinal polypeptide in neurosecretory vesicles of submucous neurons in the rat jejunum.

The localization of vasoactive intestinal polypeptide and neuropeptide Y in submucous nerves of rat jejunum was studied using both single-label pre-embedding immunocytochemistry and post-embedding double-label immunogold techniques. Vasoactive intestinal polypeptide-immunoreactive fibres and cell bodies were regularly observed in submucous plexus and a similar distribution was seen for neuropeptide Y. Varicose fibres were observed in single-label studies and when areas of specific interest were subjected to double-label immunogold protocols these immunoreactive profiles exhibited vesicles clearly stained for both vasoactive intestinal polypeptide and neuropeptide Y. Synaptic vesicles in immunopositive fibres observed close to the mucosa (and elsewhere in the submucosa) were dense-cored with an average diameter of 80 nm. Nerves associated with vascular elements only stained for neuropeptide Y, not for vasoactive intestinal polypeptide. These findings suggest that these two unrelated enteric peptides are co-released in the vicinity of the mucosal lining and the likely implications of such co-release are discussed.

Animals↗

The effect of deprenyl and tocopherol on cognitive performance in early untreated Parkinson's disease. Parkinson Study Group.

We conducted prospective cognitive assessments over 14 +/- 6 (mean +/- SD) months of observation as part of the multicenter trial Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP), which involved 800 patients with early untreated Parkinson's disease. We administered tests that measured memory, visuospatial, and frontal lobe functions. Subjects were randomly assigned to receive placebo, deprenyl (10 mg/d), tocopherol (2,000 IU/d), or both deprenyl and tocopherol. We analyzed treatment effects using annualized rates of cognitive change. We performed exploratory analyses to identify potential clinical and demographic correlates of cognitive performance. There was no significant effect of either deprenyl or tocopherol on cognitive test performance. In early untreated Parkinson's disease, cognitive performance appears to be stable and unrelated to either motor deterioration or treatment with deprenyl or tocopherol.

Aged↗

Blockade of complement activation prevents local and pulmonary albumin leak after lower torso ischemia-reperfusion.

Lower torso ischemia and reperfusion leads to both local and remote tissue injuries. The purpose of this study was to assess the role of complement in mediating the local and remote microvascular permeability after bilateral hind limb tourniquet ischemia. Four hours of ischemia and 4 hours of reperfusion produced an increased skeletal muscle permeability index (muscle/blood 125I albumin ratio) of 2.90 +/- 0.35 compared with the index in nonischemic muscle of 0.25 +/- 0.02 (p < 0.01). Muscle wet-to-dry-weight ratio increased from 3.93 +/- 0.04 in sham to 5.55 +/- 0.09 in ischemic muscle (p < 0.0001). Lung permeability rose at 4 hours as indicated by the increased bronchoalveolar lavage (BAL)/blood 125I albumin ratio 4.36 +/- 0.41 x 10(-3) versus sham 2.64 +/- 0.28 x 10(-3) (p < 0.05) and neutrophil sequestration 0.28 +/- 0.02 U/g myeloperoxidase (MPO) versus sham 0.14 +/- 0.02 U/g (p < 0.001). Serum lytic activity of the classical but not the alternate complement pathway was reduced. The soluble complement receptor (sCR1) was used to inhibit complement activity and attenuated the increase in the permeability index after reperfusion in ischemic muscle 1.11 +/- 0.08 (p < 0.01) and reduced the lung BAL/blood 125I albumin ratio to sham levels 2.46 +/- 0.39 x 10(-3) (p < 0.05) at 6 mg/animal, without reducing the lung neutrophil sequestration, 0.24 +/- 0.02 U/g. The authors conclude that complement activation occurred during tourniquet ischemia and mediated permeability changes in the ischemic muscle and the lungs during reperfusion.

Albumins↗

Interferon-gamma induced by administration of recombinant interleukin-2 to patients with cancer: kinetics, dose dependence, and correlation with physiological and therapeutic response.

The administration of recombinant interleukin-2 as an i.v. bolus at dose levels of from 1 to 30 MIU/m2 to patients with cancer induces easily measurable serum interferon-gamma levels of 1 to 500 U/ml. After a lag of 1 h, interferon-gamma rises to a maximum at 4 h and then slowly decreases. The peak values are poorly correlated with the dose of interleukin-2, and thus must be also be dependent on other factors. Successive administration of interleukin-2 typically increases the peak level of interferon-gamma fourfold, but does not diminish the lag period. Peak levels of interferon-gamma are also increased by concurrent administration of interferon-beta with interleukin-2. Continuous i.v. infusion of 1.5 to 20 MIU/m2 of interleukin-2/day results in interferon-gamma levels of 1 to 7 U/ml. Hypotension, which is characteristically associated with interleukin-2 administration, is correlated with interferon-gamma levels in only some patients. There was no apparent correlation between tumor regression and serum interferon-gamma levels.

Blood Pressure↗

A phase I trial of recombinant tumor necrosis factor (rTNF) administered by continuous intravenous infusion in patients with disseminated malignancy.

rTNF was administered to 28 patients with advanced metastatic cancers by continuous intravenous infusion for 5 consecutive days every 2 weeks. The dose levels were 30, 40, 70, 110, 180 and 290 micrograms/M2/day. Groups of 3 patients were started at each successive dose level and then on subsequent courses treated with the next dose level through 4 escalations as tolerated. Tumor types were: colon cancer 14; adenocarcinoma of unknown primary, 2; renal cancer, 2; leiomyosarcoma, 2; lung cancer, 1; prostate cancer, 1; thymona, 1; bladder cancer; 1; parotid, 1; Kaposi's sarcoma 2; ovarian 1. Toxicities included fever and chills (usually within the first 8 hours of infusion), fatigue, headache, decreased performance status, hypotension and CNS. All patients experienced leukopenia and thrombocytopenia within 24 hours or less after start of infusion with return of baseline by 72 hours after rTNF was stopped. The fall in these counts averaged 50% and was not dose related. No major changes in liver or renal function, coagulation or blood lipids were seen. Major dose limiting toxicities were fatigue, confusion, thrombocytopenia, seizures, hypotension and decreased performance status. NK cell activity measured against K562 target cells was augmented from about 30% target cell lysis to about 70% target cell lysis over the first 7 days of treatment. Two patients, both with metastatic colon cancer showed transient, objective tumor regression which did not qualify as a partial response. One patient with ovarian cancer had a stable partial response but progressed after 13 courses of treatment. Continuous infusion of TNF can be safely administered to patients with a maximum tolerated dose of only between 30 and 40 micrograms/M2/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotoxicity Tests, Immunologic↗

Phase I trial of recombinant interleukin-2 and recombinant beta-interferon in refractory neoplastic diseases.

Interleukin-2 (IL-2) and beta-interferon (beta-IFN) are cytokines with profound immunobiological effects on T-cell and natural killer (NK) cell activity; IL-2 also induces lymphokine-activated killer (LAK) cell cytotoxicity in humans. Both lymphokines induce antineoplastic activity against several refractory tumors. This Phase I study of 50 patients assessed the toxicities, maximally tolerated dose (MTD), effects on certain immune effector cells, pharmacokinetics of IL-2, and development of antibodies to the combination of subcutaneously administered IL-2 and intravenously administered beta-IFN. Fever was common. Indomethacin reduced the incidence and severity of fever and was necessary to prevent it from becoming dose-limiting. Hypotension occurred but never required pressors or produced complications. Constitutional symptoms, local skin toxicity at the site of IL-2 injection, generalized desquamation, eosinophilia, nausea, and vomiting were also observed. One patient had reversible renal dysfunction. Two patients experienced drug-related dyspnea without evidence of capillary leak syndrome; neither required intubation. Fluid retention and cardiotoxicity were not observed. The MTD was 5 x 10(6) U/m2 s.c. of IL-2 and 2 x 10(6) U/m2 i.v. of beta-IFN when given in combination. Enhancement of in vivo NK cell cytotoxicity and proliferation of T4+, T8+, and NK cells occurred. In vivo induction of LAK cell cytotoxicity was observed in three patients. Four patients developed nonneutralizing anti-IL-2 IgG antibodies, but none developed antibodies to beta-IFN. Peak IL-2 serum levels typically occurred 4 h following drug administration. Serum levels were within a factor of 3 of the peak level in the period studied, 1-6 h postinjection. No complete responses occurred. One patient with rectal cancer and one with transitional cell carcinoma each had a partial response, and 13 other patients (5 with renal cell, 4 with colorectal, and 4 other cancers) had stable disease. Induction of NK cell cytotoxicity was seen more commonly in patients with stable disease than in those with progressive disease. Combined administration of these agents is feasible with acceptable toxicity, and Phase II trials are warranted.

Adult↗

Butyrate infusions in the ovine fetus delay the biologic clock for globin gene switching.

The switch from fetal to adult hemoglobin expression is regulated in many mammalian species by a developmental clock-like mechanism and determined by the gestational age of the fetus. Prolonging fetal globin gene expression is of considerable interest for therapeutic potential in diseases caused by abnormal beta-globin genes. Butyric acid, which is found in increased plasma concentrations in infants of diabetic mothers who have delayed globin gene switching, was infused into catheterized fetal lambs in utero during the time of the normal globin gene switch period. The globin gene switch was significantly delayed in three of four butyrate-treated fetuses compared with controls and was entirely prevented in one fetus in whom the infusion was begun before the globin switch was under way. These data provide a model for investigating and arresting the biologic clock of hemoglobin switching.

Animals↗

Preservation of freeze-dried liposomes by trehalose.

One of the practical difficulties with the frequently proposed use of liposomes for delivery of water-soluble substances to cells in whole organisms is that liposomes are relatively unstable during storage. We have studied the ability of trehalose, a carbohydrate commonly found at high concentrations in organisms capable of surviving dehydration, to stabilize dry liposomes. With trehalose both inside and outside the bilayer, almost 100% of trapped solute was retained in rehydrated vesicles previously freeze-dried with 1.8 g trehalose/g dry phospholipid. Trehalose is very effective at inhibiting fusion between liposomes during drying, as assessed by freeze-fracture and resonance energy transfer between fluorescent probes incorporated into the bilayer. However, inhibition of fusion alone does not account for the preservation of the dry liposomes, since the concentration of trehalose required to prevent leakage is more than 10-fold that required to prevent fusion. We provide evidence that stabilization of the dry liposomes requires depression of transition temperature and consequent maintenance of the constituent lipids in the dry liposomes in a liquid crystalline phase.

Chromatography, Gel↗

Livedo reticularis due to multiple cholesterol emboli.

Three patients with advanced atherosclerotic vascular disease developed multiple cholesterol emboli. The clinical presentation typically includes livedo reticularis of the lower part of the body and purple toes. Small areas of necrosis and ulceration may be present distally, despite palpable pulses. Muscular and abdominal pain, as well as alterations in renal function, may also occur. Cutaneous biopsy reveals characteristic cholesterol clefts within atheromatous debris filling small, deep arterial lumen. Pathophysiologic mechanisms are discussed.

Adult↗

[Magnifying vision aids and their use by vision-handicapped patients].

Patients with visual acuities of below 0.4 at both long and short range cannot be sure of seeing well enough to read or watch TV. Low-vision aids improve vision to a such a degree that these activities can be performed once again. However, aside from this positive effect, low-vision aids have some disadvantages which sometimes prevent patients from actually using them. An investigation conducted among 150 patients revealed that 84% of them used their low-vision aids for about an hour or so a day.

Adolescent↗