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Biomedical subjects

J Madsen

Publications and source records attributed to J Madsen.

At least 55 records · Page 3Linked to original sources
PubMed1996

The critical importance of stimulus intensity in intraoperative monitoring for partial dorsal rhizotomy.

During partial lumbosacral dorsal rhizotomy (PDR), intraoperative dorsal rootlet stimulation (drs) evokes motor responses, presumed to be reflexes, which are used to select rootlets for section. However, dr stimuli may also costimulate ventral root (vr) and evoke an M rather than a reflex response, the two being distinguishable only by comparison of response latencies after drs at two separate sites. In 15 consecutive spastic cerebral palsy patients undergoing PDR, we asked whether reflex and M responses were distinguishable on the basis of stimulus intensity (SI). For soleus H reflexes evoked by percutaneous tibial nerve stimulation, the SI for reflex afferents was usually subthreshold for exciting motor fibers. Similarly, for nerve roots, reflexes were evoked by drs at SIs generally less than that for M responses evoked by vr stimulation (vrs). In contrast, M responses evoked by drs required SIs that were on average 20 times greater. Finally, costimulation of contralateral vr after ipsilateral vrs occurred at SIs shown to evoke M responses after drs. We conclude that: (1) reflex and M responses evoked by drs are distinguishable on the basis of the required SI; and (2) drs employing SIs greater than required for vrs evokes M rather than reflex responses due to costimulation of ipsilateral and contralateral vr.

Cerebral Palsy↗
PubMed1996

Lamotrigine high-dose tolerability and safety in patients with epilepsy: a double-blind, placebo-controlled, eleven-week study.

PURPOSE: This study was undertaken to evaluate the dose tolerability and safety of a chronic ascending twice-daily (b.i.d.) dosage regimen of < or = 700 mg/day lamotrigine (LTG) and to include determination of the LTG pharmacokinetic profile at doses > or = 500 mg/day in patients receiving concomitant enzyme-inducing antiepileptic drugs (AEDs). METHODS: Twelve adult male epileptic patients treated with enzyme-inducing AEDs received < or = 700 mg/day (b.i.d.) oral LTG (n = 8) or placebo (controls, n = 4). For 3 weeks, as outpatients they had their LTG dosage increased from 100 to 400 mg/day. Then, in a clinical research study unit, patients received regimens of 500, 600, and 700 mg/day for 1 week each. Controls received matching placebo in the same sequence. At study end, dosages were tapered in 2 weeks. Follow-up evaluations were made 7 days later. RESULTS: Five LTG patients tolerated 700 mg/day for 1 week. LTG was reduced to 600 mg/day in a patient with mild diplopia and to 500 mg/day in a patient with mild oscillopsia and diplopia. One patient discontinued 300 mg/day therapy with a moderately intense diffuse papular skin rash, attributed to LTG. Headache, drowsiness, faintness, and diplopia, the common adverse events (AEs), were mild to moderate in intensity and occurred in 50-75% of patients in both groups (except for diplopia, occurring only with LTG). Concomitant AED plasma concentrations were not markedly changed by LTG. LTG pharmacokinetics were linear over the range of 500-700 mg/day. CONCLUSIONS: LTG doses < or = 700 mg/day can be tolerated in patients receiving concomitant enzyme-inducing AEDs.

Adolescent↗
PubMed1996

Human HLA-B27 gene enhances susceptibility of rats to oral infection by Listeria monocytogenes.

Germfree rats transgenic for the human genes HLA-B27 and beta 2-microglobulin were colonized with hemolysin-positive (Hly+) or hemolysin-negative (Hly-) strains of Listeria monocytogenes. HLA-B27 rats were very susceptible to infection with Hly+ L monocytogenes none survived beyond 6 days. Conversely, nontransgenic control rats survived alimentary tract colonization with the Hly+ strain, and both transgenic and nontransgenic rats survived colonization with the Hly- strain of L monocytogenes. After colonization with Hly+ L monocytogenes, both transgenic and nontransgenic rats developed severe bowel inflammation which consisted histologically of microab scesses, granulomatous lesions, and ulcers; however, whereas the transgenic rats died within 6 days, only very mild intestinal lesions were seen in nontransgenic rats 10 to 42 days after colonization. Liver and splenic lesions were small and transient in nontransgenic rats. Transgenic and nontransgenic control rats infected with Hly- Listeria developed mild transient diarrhea but showed no histological changes in the intestine. This study thus documents an association between a particular bacterial product (hemolysin produced by L monocytogenes) and the induction of severe inflammatory disease and death in rats expressing HLA-B27 and beta 2-microglobulin.

Administration, Oral↗
PubMed1995

Liposomal vaccines.

Liposomes have been used therapeutically to deliver drugs to certain anatomical sites. The use of liposomes to deliver antigens, although not a new concept, has received less attention. At least two vaccines of nearly identical liposome base composition to our vaccines have been tested in humans. A malaria vaccine study showed that the liposomal preparation is quite safe: reaction profiles of volunteers receiving the vaccine demonstrated little reactivity and virtually no pyrogenicity (14). The concentration of MPLA in the vaccine was substantially higher (nearly 50,000 times) than the pyrogenic dose of free lipid A. The same vaccine, but different antigen (gp120, an HIV protein), was tested in volunteers and had the same lack of toxicity (27). In both studies, antibodies and cytotoxic cells specific for the respective antigens were produced. We have several subunit vaccines under development for infectious diseases (gram negative sepsis, fungal infections, protozoan infections), metabolic disorders (hypercholesterolemia, diabetic retinopathy, macular degeneration), and neoplastic diseases (multi-drug resistant cancer, primary and metastatic tumors, and angiogenic hyperproliferative disorders). In each case, one or more antigens were identified that might be useful in immunologic control of biologic proliferation (i.e., pathogen or tumor growth, rise in serum cholesterol, growth of blood vessels). We anticipate that at least one of these vaccines will be ready for testing in humans in the next calendar year.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Antibody and cytotoxic T-lymphocyte responses to a single liposome-associated peptide antigen.

The development of peptide-based vaccines that elicit antibody (Ab) and cellular immune responses has been hampered by the lack of highly immunogenic formulations. In this study, we compared the induction of Ab and cytotoxic T-lymphocyte (CTL) responses to a peptide derived from the V3 loop of HIV-1 gp120 (P18 and its cysteine-glycine derivative (CG-P18)) when incorporated into liposomes with lipid A (LA) or mixed with aluminum hydroxide. P18-specific CTL were only observed with liposomes with LA. P18-specific Ab responses were found with liposomes containing CG-P18 but not P18. Increased surface expression of the former, resulted in enhancement of the Ab response without loss of CTL induction. Thus, the manner in which a peptide is localized can influence the outcome of the response induced by highly immunogenic liposome formulations.

Amino Acid Sequence↗
PubMed1995

The temporal-distance effect in subjects with dementia of the Alzheimer type.

The efficacy of temporal-distance processing for spatial locations was evaluated in college students, elderly controls, and subjects with mild and moderate dementia of the Alzheimer type (DAT). The elderly controls showed a slightly lower level of performance than college students, but both elderly controls and college students displayed a temporal-distance effect. The mild DAT subjects performed the task accurately only at the greatest temporal distances. The moderate DAT subjects performed at chance levels for all distances. Because similar changes in the temporal-distance function have been described for humans and animals with small hippocampal or prefrontal cortex damage, there might be important hippocampal or prefrontal cortex involvement or both in early stages of Alzheimer disease.

Adult↗
PubMed1995

A vaccine-elicited, single viral epitope-specific cytotoxic T lymphocyte response does not protect against intravenous, cell-free simian immunodeficiency virus challenge.

Protection against simian immunodeficiency virus (SIV) challenge was assessed in rhesus monkeys with a vaccine-elicited, single SIV epitope-specific cytotoxic T-lymphocyte (CTL) response in the absence of SIV-specific antibody. Strategies were first explored for eliciting an optimal SIV Gag epitope-specific CTL response. These studies were performed in rhesus monkeys expressing the major histocompatibility complex (MHC) class I gene Mamu-A*01, a haplotype associated with a predominant SIV CTL epitope mapped to residues 182 to 190 of the Gag protein (p11C). We demonstrated that a combined modality immunization strategy using a recombinant Mycobacterium bovis BCG-SIV Gag construct for priming, and peptide formulated in liposome for boosting, elicited a greater p11C-specific CTL response than did a single immunization with peptide-liposome alone. Vaccinated and control monkeys were then challenged with cell-free SIVmne by an intravenous route of inoculation. Despite a vigorous p11C-specific CTL response at the time of virus inoculation, all monkeys became infected with SIV. gag gene sequencing of the virus isolated from these monkeys demonstrated that the established viruses had no mutations in the p11C-coding region. Thus, the preexisting CTL response did not select for a viral variant that might escape T-cell immune recognition. These studies demonstrate that a potent SIV-specific CTL response can be elicited by combining live vector and peptide vaccine modalities. However, a single SIV Gag epitope-specific CTL response in the absence of SIV-specific antibody did not provide protection against a cell-free, intravenous SIV challenge.

Animals↗
PubMed1995

Effect of SF6-O2 (80/20) breathing on air bubbles in rat tissues.

We studied the effect of SF6-O2 breathing on air bubbles injected into skeletal muscle, rat-tail tendon, the anterior chamber of the eye, and spinal white matter. Decompression-induced nitrogen bubbles in adipose tissue were studied during breathing of SF6-O2 (80/20). The results of SF6-O2 breathing are compared with previous experiments using heliox (80/20) as the breathing medium. Bubbles studied in skeletal muscle, eye chamber, and spinal white matter were found to behave in a two-phased manner during SF6-O2 (80/20) breathing. All bubbles would initially decrease rapidly in size for a period of 10-80 min (depending on the tissue). Subsequently, the bubbles stabilized and decreased in size with a shrinking rate near zero. In spinal white matter, very small bubbles decreased size with a shrinking rate near zero. In spinal white matter, very small bubbles could disappear before development of the slow phase. All bubbles in tendon shrank at a rather constant rate during SF6-O2 (80/20) breathing until they disappeared. During SF6-O2 (80/20) breathing, all bubbles in adipose tissue shrank and disappeared at least as fast as during heliox (80/20) breathing. Just before disappearance of the bubbles the shrinking rate slowed. Comparison of the effects of SF6-O2 (80/20) and heliox (80/20) breathing suggests that countercurrent gas exchange is at work in some tissues.

Adipose Tissue↗
PubMed1994

[Venous gas embolisms].

The risk of creating a venous gas embolism (VGE) exists, whenever surgery is performed in areas where venous pressures are below atmospheric pressure, or when the pressure of an insufflation gas exceeds venous pressures. Anaesthesia using N2O should be avoided in these situations. The patients should be monitored by systems offering sensitivity and specificity: Doppler, ECHO, ETCO2 and PAP-measurements are the methods providing the highest sensitivities. ETCO2 monitoring is recommendable. In addition, attention should be directed towards common clinical signs: Tachypnoea, tachycardia, systemic hypotension, cardiac arrhythmias and cardiac "mill wheel" murmurs. When a diagnosis of VGE is made, further embolization must be avoided. Let the patient inhale pure oxygen. Attempt to aspirate gas through a central venous line. Put the patient in a combined Durant's and Trendelenburg's position. (During caesarean section however, use the anti-Trendelenburg's position.) Consider hyperbaric oxygen treatment in case of arterial gas embolism.

Anesthetics, Inhalation↗
PubMed1994

24-hour energy expenditure and substrate oxidation rates are unaffected by body fat distribution in obese women.

Twenty-four-hour energy expenditure (EE) and nonprotein respiratory quotient (RQnp) were measured by indirect calorimetry in 19 upper-body-obese (UBO) and 15 lower-body-obese (LBO) women with similar body mass index (BMI) and body fat percent. The measurements were performed in a respiration chamber on a predetermined physical activity program and a controlled diet. No differences between the UBO and LBO groups were found in 24-hour, daytime, and sleeping EE after adjustment for differences in fat-free mass (FFM). Furthermore, no group effect was observed in RQnp, but a positive correlation was found between RQnp and age. Despite the fact that an increased free fatty acid (FFA) turnover has been found in UBO subjects, the present study does not support the contention that upper-body obesity is accompanied by an increased lipid oxidation.

Adipose Tissue↗
PubMed1994

Insulin sensitivity in post-obese women.

1. Both increased and decreased sensitivity to insulin has been proposed to precede the development of obesity. Therefore, insulin sensitivity was measured during a 2 h hyperinsulinaemia (100 m-units min-1 m-2) euglycaemic (4.5 mmol/l) glucose clamp combined with indirect calorimetry in nine weight-stable post-obese women and in nine matched control women preceded by 12 h fasting after 48 h on a standardized diet. 2. Both glucose disposal rate (post-obese women, 9.5 +/- 2.2 mg min-1 kg-1, control women, 11.2 +/- 1.4 mg min-1 kg-1, not significant) and glucose oxidation (3.6 +/- 0.5 mg min-1 kg-1 versus 4.0 +/- 0.7 mg min-1 kg-1, not significant) were similar in the two groups during the last 30 min of the clamp. Lipid oxidation also decreased similarly during the clamp in the post-obese women (from 30.4 +/- 12 to 2.0 +/- 7 J min-1 kg-1) and in the control women (from 33.6 +/- 11 to 5.4 +/- 8 J min-1 kg-1, not significant). Basal plasma concentrations of free fatty acids were similar, but at the end of the clamp free fatty acids were lower in the post-obese women than in the control women (139 +/- 19 and 276 +/- 48 mumol/l, P = 0.02). 3. We conclude that the insulin sensitivity of glucose metabolism is unaltered in the post-obese state. The study, however, points to an increased antilipolytic insulin action in post-obese subjects, which may favour fat storage and lower lipid oxidation rate postprandially.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Decreased postprandial thermogenesis and fat oxidation but increased fullness after a high-fiber meal compared with a low-fiber meal.

The effect of a high-fiber (4.7 g/MJ) and an isoenergetic low-fiber (1.7 g/MJ) meal on 6-h postprandial thermogenesis, substrate metabolism, hormones, and satiety was investigated in 10 healthy, normal-weight male subjects. Diet-induced thermogenesis (DIT) was significantly reduced after the high-fiber meal (416.4 +/- 28.6 kJ/6 h) compared with the low-fiber meal (498.5 +/- 23.1 kJ/6 h; ANOVA: P < 0.0001), as was postprandial fat oxidation (P < 0.0001). The difference in DIT was correlated with the different palatability of the test meal (r = 0.89, P < 0.01). No differences were observed in plasma concentrations of glucose, insulin, norepinephrine, epinephrine, or gastrointestinal hormones, but C-peptide increased less (P < 0.05) and nonesterified fatty acids decreased more (P < 0.05) after the high-fiber meal. Finally, fullness was increased and desire to eat decreased after the high-fiber meal (P < 0.0001). In conclusion, a high-fiber meal decreased DIT and fat oxidation but increased fullness compared with a low-fiber meal.

Adult↗