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Biomedical subjects

S Rose

Publications and source records attributed to S Rose.

At least 145 records · Page 8Linked to original sources
PubMed1996

Repeated administration of escalating high doses of dexfenfluramine does not produce morphological evidence for neurotoxicity in the cortex of rats.

Rats were treated for 28 days with increasing doses of dexfenfluramine (0.5, 1, 1.5, 2, 3, 4 and 5 mg/kg bid ip, each dose given for 4 days before being increased) and subsequently studied at intervals between 1 and 60 days following the cessation of treatment. Control rats received vehicle and were allowed food ad libitum or were pair fed with dexfenfluramine-treated animals. Immediately following drug treatment 5-HT immunoreactivity was increased in cortical areas compared to control animals. Subsequently, there was a persistent decrease in fine fibre density and the appearance of coarse truncated fibres. 5-HT levels in cortex were decreased 1 day following dexfenfluramine treatment but recovered to control values by 15 days. GFAP and GAP 43 immunoreactivity was unaffected by dexfenfluramine treatment compared to control animals, indicating a lack of evidence for neuronal degeneration and regeneration. Dexfenfluramine treatment decreased the density of 5-HT uptake sites in the cortex, labelled with [3H]-citalopram, but this partially recovered towards control values at 60 days. These alterations in 5-HT terminal networks conflict with the return of 5-HT levels to normal and the lack of evidence for degenerative changes or neuronal regrowth. On the basis of these results, it cannot be concluded that dexfenfluramine is neurotoxic.

Animals↗
PubMed1996

Abnormal reflex venous function in patients with neuromediated syncope.

OBJECTIVES: We sought to compare the forearm reflex venous response to mental arithmetic stress in patients with neuromediated syncope and in normal subjects. BACKGROUND: Patients with neuromediated syncope have a paradoxic arterial vasodilation in response to stressors that usually provoke vasoconstriction. Given the postulated role of diminished preload in provoking the reflex responses resulting in syncope, we hypothesized that mental stress might provoke paradoxic reflex venodilation in patients with neuromediated syncope. METHODS: Twelve normal subjects (mean age [+/-SD] 47 +/- 9 years) and 27 patients with neuromediated syncope (mean age 42 +/- 13 years) were studied before and during a mental arithmetic stress test. Forearm venous pressure-volume relations were determined by using radionuclide plethysmography. RESULTS: During mental arithmetic stress, heart rate and systolic and diastolic blood pressure increased significantly and similarly both in normal subjects and in patients with neuromediated syncope. The heart rate and blood pressure changes were qualitatively similar in both groups. However, with mental arithmetic stress, forearm venoconstriction of 13 +/- 2% (mean +/- SEM) was noted in normal subjects (p < 0.001) but not in patients with neuromediated syncope (mean 2%, p = NS). This group response of patients with neuromediated syncope did not result from a lack of individual responses but occurred because these patients had a wide range of responses. The normal physiologic and methodologic variability of the method was +/- 4%. Thirteen of the 27 patients with neuromediated syncope had forearm venoconstriction of 14.5 +/- 6.8% during mental arithmetic stress, whereas 7 had paradoxic forearm venodilation of 14.6 +/- 8.8%, and 7 were considered nonresponders (-1.3 +/- 3.4%). Thus, 14 (52%) of the 27 patients with syncope did not have normal vasoconstriction in response to mental stress. CONCLUSIONS: Patients with neuromediated syncope have an abnormal range of forearm venomotor responses to mental arithmetic stress. Reflex control of the veins may play an important role in the pathogenesis of neuromediated syncope.

Adult↗
PubMed1996

Gastrointestinal manifestations of scleroderma.

The gastrointestinal tract is commonly involved in SSc. The esophagus is the most frequently affected, followed by the anorectal region, the small bowel, stomach, and colon. Smooth muscle atrophy and to a lesser degree fibrosis is the underlying defect responsible for the resulting abnormalities. These smooth muscle alterations have a significant impact on gastrointestinal motility, which results in secondary disorders of GER, pseudo-obstruction, bacterial overgrowth, and disordered bowel functions. The clinical presentation for these conditions ranges from asymptomatic to life-threatening. Thus, gastrointestinal evaluation and treatment of these conditions is an important aspect in the management of patients with SSc.

Colonic Diseases↗
PubMed1996

Development and optimization of the human allogeneic mixed lymphocyte islet (MLIC) and acinar (MLAC) coculture system.

Although human islet allotransplantation has been shown to be effective in restoring normoglycaemia to diabetic recipients, the long-term success rate is relatively low. The poor results of human islet transplantation are surprising given the relative ease of establishing functioning islet allografts in rodent models with minimal immunosuppression and have been attributed to a number of factors of which rejection may play a major part. The impracticality of studying the immunogenicity of human islets in vivo has led us to develop a model specifically to study the allogeneic immune response to the major components of isolated human islet preparations. To try and overcome the variability associated with this methodology, this study was designed to develop and optimize the mixed lymphocyte coculture as an in vitro model for the initial alloresponse to both freshly isolated intact human islets (MLIC) and acinar tissue pieces (MLAC). For this, titration of the islets and acinar tissue, as well as kinetic studies of the response, were used to select optimum conditions for the MLIC which were shown to be ten islets and ten acinar tissue pieces with a coculture duration of 7-9 days. The optimized studies included the use of non-tissue culture microwells to deter fibroblast growth, RPMI + 10% human AB serum to reduce the background lymphocyte response and a low concentration of dithizone to stain the islets prior to handpicking. Freshly isolated human islets were found to stimulate allogeneic lymphocytic proliferation; however, differences in the relative response to islets and acinar tissue led us to test the effect of soluble products from the acinar cells on lymphocyte proliferation in the mixed lymphocyte reaction. An inhibitory effect of the soluble products of acinar cells on the allogeneic lymphocyte proliferative response was found to contribute to the reduced response of the MLAC compared to the MLIC. Human islets were shown to stimulate an allogeneic immune response in vitro, and this MLIC model provides a method for assessing the specific immunogenicity of human isolated islet preparations and associated acinar tissue in transplantation.

Coculture Techniques↗
PubMed1996

Alterations in peptide levels in Parkinson's disease and incidental Lewy body disease.

The levels of the neuropeptides Met- and Leu-enkephalin (MET-ENK, LEU-ENK), substance P and neurotensin were measured by a combined high performance liquid chromatography/radioimmunoassay (HPLC/RIA) method in postmortem samples of basal ganglia from Parkinson's disease patients, incidental Lewy body disease patients (pre-symptomatic Parkinson's disease) and matched controls. Dopamine (DA) levels were reduced in the caudate nucleus and putamen in Parkinson's disease, but unaltered in incidental Lewy body disease. The levels of MET-ENK were reduced in the caudate nucleus, putamen and substantia nigra in Parkinson's disease. Met-enkephalin levels were reduced in the caudate nucleus and in the putamen in incidental Lewy body disease. Leu-enkephalin levels were decreased in the putamen and were undetectable in the substantia nigra in Parkinson's disease. Leu-enkephalin levels were unchanged in incidental Lewy body disease, although there was a tendency to a reduction in putamen. Substance P levels were reduced in the putamen in Parkinson's disease. No significant changes in substance P content were observed in incidental Lewy body disease. Neurotensin levels were increased in the substantia nigra in Parkinson's disease. Neurotensin levels in incidental Lewy body disease were not altered significantly, but tended to parallel the changes in Parkinson's disease. The changes in basal ganglia peptide levels in incidental Lewy body disease generally followed a trend similar to those seen in Parkinson's disease, but were less marked. This suggests that they are an integral part of the pathology of the illness and not secondary to DA neuronal loss or a consequence of prolonged drug therapy.

Aged↗
PubMed1996

Percutaneous versus open tracheostomy: a retrospective cohort outcome study.

Percutaneous tracheostomy has been advocated as a faster, safer, and less invasive method of placing tracheostomy tubes in ventilated patients. To compare outcome differences, as measured by complication rates, between percutaneous and open tracheostomy, a retrospective cohort study was performed. All procedures were performed in the intensive care unit of a university-affiliated hospital. The minor complication rates did not differ significantly between percutaneous and open tracheostomy (12/31 vs. 12/29, respectively; p > 0.05), nor did there appear to be a difference in rates of major complications between the two groups (7/31 vs. 5/29; p > 0.05). This study identified a trend towards an increased risk of delayed airway loss in the percutaneous tracheostomy group.

APACHE↗
PubMed1996

The Stretching Window Part Two: Rate of Thermal Decay in Deep Muscle Following 1-MHz Ultrasound.

Thermal ultrasound can be effective in increasing extensibility of collagen, thus aiding joint mobilization and stretching. In 1995, we reported on the rate of temperature decay following 3-MHz ultrasound in subcutaneous tissues. We repeated that study at 1-MHz frequency to see if the stretching window is different for deep muscle. Twenty subjects had two 23-gauge thermistors inserted 2.5 cm and 5 cm deep into their triceps surae muscle. We administered 1-MHz continuous ultrasound at 1.5 W/cm(2) until the tissue temperature increased 4 degrees C (vigorous heating). Immediately following the treatment, we recorded the rate at which the temperature dropped at 30second intervals. We ran a stepwise nonlinear regression analysis to predict temperature decay as a function of time following ultrasound treatment. There was a significant nonlinear relationship between time and temperature decay. At 2.5 cm, the average time for the temperature to drop each degree was: 1 degrees C = 2:34; 2 degrees C = 6:35; 3 degrees C = 12:10: and 4 degrees C = 21:14. At 5 cm, the average time for the temperature to drop each degree was: 1 degrees C = 2:31, 2 degrees C = 6:50: 3 degrees C = 14:32; and 4 degrees C = 27:49. Based upon prior research, thermal decay of 1-MHz ultrasound was slower than 3 MHz, and the deeper tissue cooled at a slower rate than superficial tissue following 1-MHz ultrasound. The data illustrated that the stretching window was open longer for deep-seated structures than for superficial ones.

Journal Article↗
PubMed1996

[Pathophysiology of polytrauma].

Sequential organ failure after multiple trauma emerges from a whole-body inflammatory process which develops as a complex host defense response to hypovolemic shock/resuscitation and traumatic tissue injury. Successful prevention and treatment involves exact assessment of inflicted damage and profound knowledge of the different stages of posttraumatic immune alterations. Local release of potent inflammatory mediators (cytokines, complement, arachidonic acid derivatives, reactive oxygen metabolites) primarily induces a repair process. However, massive soft tissue and bone injury, follow-up surgery, infections and blood transfusions trigger a systemic spill over of these mediators orchestrating a generalized inflammatory response (Systemic Inflammatory Response Syndrome, SIRS). Diffuse capillary leakage and microcirculatory disorder prepare cellular dysfunction. Secondary severe immune defects support septic complications which maintain an autodestructive process. Therapeutical advances depend on the analysis of local and time-dependent expression of relevant inflammatory mediators and cellular signalling systems.

Arachidonic Acid↗
PubMed1996

[Spiral CT of the thorax in primary diagnosis and intensive treatment of polytrauma patients].

The performance of a rapid spiral chest CT scan during primary diagnosis and intensive care leads, in a high percentage of cases, to clinically relevant diagnoses. In particular, occult ventral (tension-) pneumothoraces and lung contusions have been found in one third of polytraumatized patients both initially and during the sequential course. Additional insertion of chest tubes has been observed to be the major consequence.

Adult↗
PubMed1995

Major histocompatibility complex class II DR alleles DRB1*1501 and those encoding HLA-DR13 are preferentially associated with a diminution in maternally transmitted human immunodeficiency virus 1 infection in different ethnic groups: determination by an automated sequence-based typing method.

Transmission of human immunodeficiency virus 1 (HIV-1) from an infected women to her offspring during gestation and delivery was found to be influenced by the infant's major histocompatibility complex class II DRB1 alleles. Forty-six HIV-infected infants and 63 seroreverting infants, born with passively acquired anti-HIV antibodies but not becoming detectably infected, were typed by an automated nucleotide-sequence-based technique that uses low-resolution PCR to select either the simpler Taq or the more demanding T7 sequencing chemistry. One or more DR13 alleles, including DRB1*1301, 1302, and 1303, were found in 31.7% of seroreverting infants and 15.2% of those becoming HIV-infected [OR (odds ratio) = 2.6 (95% confidence interval 1.0-6.8); P = 0.048]. This association was influenced by ethnicity, being seen more strongly among the 80 Black and Hispanic children [OR = 4.3 (1.2-16.4); P = 0.023], with the most pronounced effect among Black infants where 7 of 24 seroreverters inherited these alleles with none among 12 HIV-infected infants (Haldane OR = 12.3; P = 0.037). The previously recognized association of DR13 alleles with some situations of long-term nonprogression of HIV suggests that similar mechanisms may regulate both the occurrence of infection and disease progression after infection. Upon examining for residual associations, only only the DR2 allele DRB1*1501 was associated with seroreversion in Caucasoid infants (OR = 24; P = 0.004). Among Caucasoids the DRB1*03011 allele was positively associated with the occurrence of HIV infection (P = 0.03).

Acquired Immunodeficiency Syndrome↗
PubMed1995

The rise of neurogenetic determinism.

Dramatic advances in neuroscience are changing and enriching our understanding of brain and behaviour. But reductionist interpretations of these advances can cause great harm.

Behavior↗
PubMed1995

The effect of dosage release formulations on the pharmacokinetics of propranolol stereoisomers in humans.

Recent studies in dogs have suggested that the disposition of S- and R-propranolol may depend on the input rate of drug delivered to the liver. Therefore, this study was designed to determine whether differences in the disposition of S- and R-propranolol occur in humans when altering the input rate of propranolol by giving different dosage forms of the drug. Twelve healthy subjects were enrolled in a single-dose, 4-way crossover pharmacokinetic study in which racemic propranolol was given according to 1 of 4 treatments: one 80-mg immediate-release (IR) tablet, phase A; two 80-mg IR tablets, phase B; a 160-mg controlled-release capsule, phase C; or a 10-mg IV bolus, phase D. The results showed no significant differences in the ratios of S/R-propranolol for AUC, clearance, or overall mean concentration among the oral dosage groups. Significant differences in these parameters including Cmax S/R ratio were seen between the oral phases and the IV phase. These differences appear to be related more to the route of administration than to the low input rate. However, at high concentrations there may be input-rate alteration in S/R ratios. Specifically, for phase B, which had the highest Cmax concentrations, the Cmax S/R ratio was significantly lower than the other oral dosage groups A and C (Cmax S/R ratios: 1.44 versus 1.54 and 1.54, respectively; P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Quantitative endoscopy: precise computerized measurement of metaplastic epithelial surface area in Barrett's esophagus.

BACKGROUND/AIMS: The inability to precisely measure the area of Barrett's metaplasia has impaired the study of its natural history and response to therapy. This study used a novel computer program that creates two-dimensional maps of the esophagus allowing for calculation of the area of Barrett's metaplasia. METHODS: Endoscopic photographs of Barrett's models and patients were obtained by independent endoscopists. The program transformed the photographs into maps, and the area of Barrett's metaplasia was calculated. RESULTS: Using models, calculated areas correlated with actual areas (r = 0.96) with an overall error of 5.2%. Color, size, shape, diameter of the model, or endoscopist's experience did not affect the accuracy. Accuracy did improve by decreasing the interval between photographs from 4 cm (10.0% error) to 2 cm (4.8% error). In patients, area calculations from maps created by independent technicians correlated precisely (r = 0.99) at 1-cm (n = 22) and 2-cm (n = 40) intervals. Independent endoscopists correlated precisely in producing photographs for map construction (r = 0.99; n = 20). CONCLUSIONS: This novel computer technology produces two-dimensional maps of Barrett's metaplasia that can be used to accurately calculate area. Minimal interobserver variability in obtaining photographs is found.

Adult↗
PubMed1995

Grouping HLA-B locus serologic specificities according to shared structural motifs suggests that different peptide-anchoring pockets may have contrasting influences on the course of HIV-1 infection.

Two different groups of HLA-B specificities were associated with two contrasting outcomes of HIV-1 infection. HLA-B45, -B49, and -B50 were each found at a moderately increased frequency among individuals responding to HIV-1 infection with a marked circulating and infiltrative CD8 T-cell lymphocytosis, a slow rate of CD4 T-cell decline, very low frequency of opportunistic infections, and low viral strain heterogeneity. In contrast, among HIV-infected individuals with more rapid progression to opportunistic infections, HLA-B35 was found to be increased in frequency and to act as a dominant marker for this adverse outcome. HLA-B45, -B49, and -B50 contain identical peptide-anchoring "B" and "C-terminal" pocket structures, which differ greatly from those present in HLA-B35, implying that different immunogenic peptides are likely to be bound by these two groups of alleles. Placing HLA-B45, -B49, and -B50 into one structurally defined group revealed a much stronger and statistically significant association with the CD8 lymphocytosis syndrome (OR = 5.3, p = 0.0005). The B pocket structure in these alleles contains an easily accessible lysine residue at position 45, suggesting that the P2 or P3 anchor residue of a bound peptide is negatively charged. Additionally, by observing the effect on the ORs of adding structures containing amino acid substitutions in the C-terminal pocket of HLA-B45, -B49, and -B50, this region was also shown to influence susceptibility to this host response.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1995

Increased striatal dopamine efflux in vivo following inhibition of cerebral nitric oxide synthase by the novel monosodium salt of 7-nitro indazole.

The role of nitric oxide (NO) in striatal dopamine release has been controversial. Most NO synthase inhibitors affect more than one isoform of the enzyme and exert vasoconstrictor effects which may also affect striatal dopamine function. We now report on the effect of a soluble monosodium salt of the selective brain NO synthase inhibitor 7-nitro indazole (7-NINA). Using 7-NINA the first study of selective inhibition of the brain isoform of NO synthase on dopamine efflux in rat striatum was undertaken by use of in vivo microdialysis. Perfusion with 7-NINA (1 mM) increased striatal dopamine efflux. The effect of 7-NINA was partially antagonized (67%) by co-perfusion with L-arginine (1 mM), the precursor of NO formation in vivo. This suggests that 7-NINA induces a competitive inhibition of NO synthase activity. These data show that endogenous NO has an inhibitory effect on striatal dopamine efflux in vivo.

Amino Acid Oxidoreductases↗
PubMed1995

Esters of L-dopa: structure-hydrolysis relationships and ability to induce circling behaviour in an experimental model of hemiparkinsonism.

A number of carboxylate esters of L-dopa, some of which are novel, were examined for their physicochemical and biological properties. A few esters of tyrosine and phenylalanine were included for comparison. The compounds displayed great differences in their lipophilicity and stability towards chemical and enzymatic (human plasma) hydrolysis. Within subseries, relationships exist between structural properties and rate constants of chemical or enzymatic hydrolysis. In an experimental model of hemiparkinsonism (circling behaviour in rats), some of the L-dopa esters (the isopropyl, sec-butyl and 2-(tetrahydropyranyl)methyl esters) showed an activity distinctly greater than that of L-dopa, although the difference was not statistically significant.

Animals↗