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Biomedical subjects

A Miller

Publications and source records attributed to A Miller.

At least 253 records · Page 14Linked to original sources
PubMed1995

Fatigue therapy in multiple sclerosis: results of a double-blind, randomized, parallel trial of amantadine, pemoline, and placebo.

OBJECTIVE: To determine the relative efficacy of amantadine, pemoline, and placebo in treatment of multiple sclerosis (MS)-related fatigue. BACKGROUND: Fatigue is a complication of MS. Both pemoline and amantadine have been used to treat MS fatigue, but their relative efficacy is not known. METHODS: Amantadine, pemoline, and placebo were compared in a randomized, double-blind, placebo-controlled study using a parallel-group design. Ninety-three ambulatory MS patients completed the study. Primary outcome measures were the fatigue severity scale (FSS); the MS-specific fatigue scale (MS-FS); and subjective response determined by verbal self-report. Secondary outcome measures consisted of assessments of sleep, depression, and vitality. Repeated-measures analysis of variance with planned post-hoc contrasts and Fisher's exact test were used to compare treatment response. RESULTS: Amantadine-treated patients showed a significantly greater reduction in fatigue, as measured by the MS-FS, than did patients treated with placebo (p = 0.04). By verbal report at the end of the study, 79% of patients treated with amantadine versus 52% treated with placebo and 32% treated with pemoline preferred drug therapy compared with no treatment (p = 0.03). No significant differences in any primary outcome measures were noted between pemoline and placebo. Neither amantadine nor pemoline affected sleep or depression relative to placebo. CONCLUSION: Amantadine was significantly better than placebo in treating fatigue in MS patients, whereas pemoline was not. The benefit of amantadine was not due to changes in sleep, depression, or neurologic disability.

Adolescent↗
PubMed1995

The influence of demographic characteristics, menopausal status, and symptoms on women's attitudes toward menopause.

The purpose of this study was to determine the influence of demographic characteristics, including ethnicity, socioeconomic status, marital status, and number of children, as well as menopausal status, physical symptoms, and psychological symptoms on midlife women's attitudes toward menopause. A random sample of 149 women, aged 35 to 65 and stratified by occupation, age, and race, was selected from employee lists. A 20-item, 7-point semantic differential Menopause Attitude Scale was administered. Menopausal status was determined by self-report and serum hormone levels of estradiol and follicle stimulating hormone (FSH). Symptoms were assessed by a 28-item Symptom Index, the Center for Epidemiologic Studies Depression Scale (CES-D) and the Bradburn Affect Balance Scale. Overall the majority of women, regardless of ethnicity or socioeconomic status, had neutral feelings toward menopause. Postmenopausal women reported the most positive attitudes toward menopause, which may indicate that once women have gone through menopause they find it to be less troubling than they anticipated earlier in life. Negative attitudes toward menopause were related to psychological symptoms with higher scores on the depression scale, suggesting that these women may be at higher risk for a difficult midlife transition.

Adult↗
PubMed1995

Cardiorespiratory responses to incremental exercise in sarcoidosis patients with normal spirometry.

Patients with sarcoidosis are known to have histologic pulmonary abnormalities despite normal lung fields or conventional pulmonary function or both. These patients permit a useful assessment of the alleged greater sensitivity of the various measurements made during incremental cardiorespiratory exercise testing. Abnormal responses on such testing may provide insight into such complaints as dyspnea in these patients. Incremental exercise testing was performed on 30 patients with biopsy-proven sarcoidosis who had normal spirometry; 13 had clear lung fields radiographically. Of these patients, the 21 who had normal single-breath diffusing capacity for carbon monoxide (Dsb; [group A]) were compared with the 9 who had decreased Dsb (group B). Half of the group A patients had excessive ventilation and 38% had increased dead space to tidal volume ratio (Vd/Vt), but frequencies of these abnormalities were greater in group B, 89 and 78%, respectively. Ventilatory response, as minute ventilation to oxygen consumption ratios ventilatory equivalents, and deadspace to tidal volume ratio (Vd/Vt) ratios were higher in group B. Widened alveolar-arterial oxygen pressure differences were seen in 7 of 9 group B patients but only 1 of 17 group A patients. This study supports the clinical impression that occult pulmonary impairment may be present in patients (in this case, sarcoidosis patients) with normal pulmonary function, and corroborates the utility of exercise testing in demonstrating such impairment. Reduction in Dsb predicted greater frequency of abnormal exercise responses, especially in oxygenation.

Adult↗
PubMed1995

The role of routine angioscopy in vascular access surgery.

PURPOSE: The purpose of this retrospective study is to describe our techniques, review our experience, and determine the feasibility, safety, and role of the routine use of angioscopy during primary and revision vascular access surgery. METHODS: Between February 1991 and October 1993, intraoperative angioscopy was routinely performed in 84 consecutive operations (51 patients) for vascular access surgery. We reviewed the videotaped recordings of the angioscopic studies together with the clinical data according to a predetermined protocol. RESULTS: There were 43 primary procedures (36 autogenous arteriovenous fistulas and 7 bridge graft fistulas) and 41 revision procedures for failed vascular access (7 autogenous arteriovenous fistulas and 34 graft bridge fistulas). In 20.9% of the primary vascular access procedures, abnormal endoluminal findings were noted. Based on these findings, only one additional intervention was performed. In revision vascular access surgery, abnormal endoluminal findings were noted in 92.7%, resulting in additional surgical interventions in 65.9% of the procedures. In the revised synthetic bridge graft fistulas, stenosis of the midgraft (n = 9) as a result of needle insertion for dialysis was more common than at venous anastomosis (n = 4). Detection and correction of endoluminal abnormalities resulted in a 30-day patency of 66.6% as opposed to 33.3% when none was detected (p < or = 0.012, Fisher's exact test). CONCLUSIONS: Routine angioscopy is technically feasible and can be performed safely in anuric patients during vascular access surgery. It provides additional and useful intraoperative information that may significantly alter the surgical procedure. Routine angioscopy may also provide new insights into the pathophysiology of vascular access failure.

Adult↗
PubMed1995

Magnetic resonance spectroscopy of the human masseter muscle in nonbruxing and bruxing subjects.

The masseter muscles of six nonbruxing subjects (five men, one woman) and six bruxing subjects (four men, two women) were assessed during chewing by nuclear magnetic resonance spectroscopy (31P-NMR). The NMR spectra were collected on a GE Sigma 1.5T whole body magnet with a double-tuned 31P/1H surface coil. Two-minute trials of rest/chewing/rest were completed three times. Averaged spectra of inorganic phosphate, phosphocreatine, and three adenosine 5' triphosphate peaks were collected in each trial. Bruxing subjects had a lower concentration of total phosphate and phosphocreatine than nonbruxing (control) subjects at rest. Bruxing subjects increased their inorganic phosphate during chewing significantly less than control subjects. The pH levels during rest and during chewing were similar in both controls and bruxers. These preliminary results suggest that bruxing subjects exhibit an altered phosphate metabolism during rest and exhibit a different phosphate metabolism pattern during chewing as compared to nonbruxing subjects.

Adenosine Triphosphate↗
PubMed1995

Schistosoma mansoni: changes in the albumen gland of Biomphalaria glabrata snails selected for nonsusceptibility to the parasite.

The LAC-line strain of the snail Biomphalaria glabrata has very low susceptibility to the parasite Schistosoma mansoni and a very low reproductive potential. Upon examination of the reproductive tract of these snails, light and electron microscopy revealed obvious abnormalities in the albumen gland. Secretory cells that are normally cuboidal in susceptible NMRI (F0) snails were squamous in LAC-line snails. These LAC-line cells contained small secretory granules and negligible rough endoplasmic reticulum and Golgi, compared to large granules and an extensive array of both organelles in F0 albumen gland cells. Comparative analyses of soluble protein extracts of F0 and LAC-line albumen glands showed several qualitative differences. Among the most prominent was an 18-kDa protein in F0 snails that was remarkably reduced in the soluble protein extracts of LAC-line snails. Also, metabolic incorporation of [35S]-methionine was impaired in LAC-line albumen glands. Whether these albumen gland changes are caused by decreased susceptibility to parasitism is yet to determined.

Animals↗
PubMed1995

Gene delivery and expression mediated by an integrin-binding peptide.

The ability to transfer sufficient DNA to specific target cells remains one of the main limitations to the development of gene therapy. For this reason much attention is being paid to the development of new gene delivery systems, both viral and non-viral. We describe gene transfer with a polycation-DNA complex which contains an integrin-binding domain. Integrin-mediated gene delivery has several potential advantages. Such complexes are less likely than other receptor-mediated gene delivery complexes to be constrained by the size of the complex. The ligands are small peptides, resembling naturally occurring integrin ligands, which minimises the possibility of complexes inducing an immune response in vivo.

Amino Acid Sequence↗
PubMed1994

Crystal structure of the extracellular region of human tissue factor.

Tissue factor is a cell-surface glycoprotein receptor which initiates the blood coagulation cascade after vessel injury by interacting with blood clotting factor VII/VIIa and which is implicated in various pathological processes. When bound to tissue factor, factor VII is readily converted to the active protease factor VIIa by trace amounts of factors Xa, IXa or VIIa. Human tissue factor consists of 263 residues, the first 219 of which comprise the extracellular region. We have determined the crystal structure of the extracellular region at a resolution of 2.2 A. Tissue factor consists of two immunoglobulin-like domains associated through an extensive, novel, interdomain interface region. The binding site for factor VII lies at the interface region and involves residues from domain 1 and an extended loop (binding 'finger') of domain 2. This is the first reported structure of a representative of the class 2 cytokine receptor family, which also includes interferon-alpha, interferon-gamma (refs 2, 3) and interleukin-10 (ref. 4) receptors.

Amino Acid Sequence↗
PubMed1994

Defective production of anti-inflammatory cytokine, TGF-beta by T cell lines of patients with active multiple sclerosis.

Activated T lymphocytes play an important role in the pathogenesis of multiple sclerosis (MS). These T cells secrete both pro- and anti-inflammatory cytokines. We have studied the production of these two kinds of cytokines by PBL of patients with MS and compared it with normal controls and other autoimmune diseases (OAD). PBL of 29 patients with MS, 14 patients with OAD, and 14 healthy normal controls were cultured for 5 wk. PBL of MS patients produced more pro-inflammatory cytokines, IL-2, IFN-gamma and TNF/lymphotoxin, and less anti-inflammatory cytokine, TGF-beta, during wk 2 to 4 in culture than PBL of normal controls. PBL of MS patients also produced more IL-2 and TNF/lymphotoxin than PBL of OAD patients. Decreased TGF-beta production by lymphocytes of patients with MS correlated directly with disease activity. MS patients with active disease produced less TGF-beta than MS patients with stable disease. The cells producing TGF-beta were primarily CD8+ T cells and CD45RA+T cells. These findings emphasize the complexity of immune response in MS patients and suggest that the increased production of pro-inflammatory cytokines by lymphocytes of patients with MS, combined with the decreased production of TGF-beta (anti-inflammatory cytokine), may play an important role in the mechanisms and manifestations of MS.

Adult↗
PubMed1994

Isolation of lysozyme-specific T cell clones that discriminate between native and denatured antigen.

Hen egg white lysozyme (HEL)-specific T cell lines and clones were generated from B6 and BDF1 mice. A variety of clonotypes were found among clones generated at an early stage (1 month) whereas fewer clonotypes were detected after several weeks of culture. Furthermore, a bulk line switched from its initial fine peptide specificity pattern (positive for fragment L2--aa. 13-105--and negative for fragment NC--aa. 1-17:Cys 6-Cys 127:120-129) to the opposite pattern (negative for L2 and positive for NC), indicating that in bulk lines, besides selection toward oligo- or monospecificity, clones previously silent can emerge after a period of time. Irrespective of early or late cloning, T cell clones could be isolated from three independent T cell lines from different mouse strains that were stimulated by either native or denatured HEL, but not both. Furthermore, 1 clone of 20 from a B6 line, 3 clones of 25 from a BDF1 line, and 1 T hybridoma clone of 10 of B10.A origin lost their capacity to respond to native HEL, yet continued to respond to reduced, carboxymethylated HEL or cyanogen bromide-cleaved, unreduced HEL. These results suggest that T cells may produce activation signals for efficient processing of native antigen.

Animals↗
PubMed1994

Audit of emergency preoperative resuscitation.

A total of 148 patients of mean age 61 years with acute gastrointestinal disease who were assessed as requiring preoperative resuscitation were studied. Overall, the mortality rate was 14.2 per cent and the morbidity rate 50.7 per cent. Resuscitation was associated with a mean(s.e.m.) improvement in predicted mortality rate of 4.2(0.8) per cent and in morbidity rate of 4.3(0.7) per cent. However, there was a group of patients in whom resuscitation was unsuccessful, despite there being no apparent difference in duration or methods of resuscitation from those of the rest of the population studied. A poor response to resuscitation was found in 28 patients; this was commoner in the elderly (P < 0.001) and in women (P < 0.05). Complications were more frequent in patients failing to improve with resuscitation (P < 0.001). In the group deteriorating despite resuscitative (P < 0.001). In the a greater proportion of patients with a perforated viscus (P < 0.001), whereas intestinal obstruction was less common (P < 0.05). This study demonstrates that resuscitation can be audited and quantified. Preoperative resuscitation appears to be beneficial, but there is a group that may benefit from synchronous surgery and resuscitation.

Acute Disease↗
PubMed1994

Orally administered myelin basic protein in neonates primes for immune responses and enhances experimental autoimmune encephalomyelitis in adult animals.

Antigen-driven tolerance is an effective method for suppression of autoimmune diseases. Adult animals can be tolerized against the induction of experimental autoimmune encephalomyelitis (EAE) by both oral and parenteral administration of myelin basic protein (MBP). We have found that in contrast to previous studies of neonatal tolerance in which parenterally administered autoantigens induced tolerance, the oral administration of MBP in neonatal rats did not result in tolerization to MBP, but instead, primed for immunologic responses. Proliferative responses to MBP and its encephalitogenic epitope were present in animals fed with MBP as neonates and co-culture of encephalitogenic T cells with cells from neonatal rats fed with MBP were associated with enhanced MBP responses rather than the suppression observed with cells from adult rats fed with MBP. Furthermore, neonates fed with MBP and immunized 6-8 weeks later with MBP in adjuvant to induce EAE revealed enhancement of disease severity, and were not protected from a second attack upon active reinduction of EAE. Subcutaneous injection of soluble MBP into neonates had no effect on EAE induction as adults, whereas intraperitoneal injection of MBP in neonates was associated with marked suppression of disease in adults. Suppression of EAE began to appear in animals fed with MBP at 4 weeks of age, and was similar to oral tolerance in adult animals when animals were fed at 6 weeks of age. These results suggest that immaturity of the immunoregulatory network associated with oral tolerance and sensitization to autoantigens via the gut in the neonatal period may contribute to the pathogenesis of autoimmune diseases.

Administration, Oral↗
PubMed1994

Antigen-driven tissue-specific suppression following oral tolerance: orally administered myelin basic protein suppresses proteolipid protein-induced experimental autoimmune encephalomyelitis in the SJL mouse.

Immunomodulatory treatment paradigms have been applied to animal models of T cell-mediated autoimmune diseases in an attempt to develop an immunospecific and non-toxic form of therapy which can be applied to humans. These treatment paradigms are often directed to T cells with a restricted T cell receptor repertoire or that react with dominant peptide determinants. Experimental data, however, suggests that even if the initial T cell response is restricted to a specific self-protein in the target organ, spreading autoimmunity may develop with broadening of T cell autoreactivity to additional epitopes of the same autoantigen or to different autoantigens in the target organ. Thus, multiple autoantigens may become targets of the autoimmune response. This makes immunotherapeutic strategies based on suppressing responses to restricted proteins or clones of cells problematic. We have previously shown that suppression of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat by oral myelin basic protein (MBP) is mediated by the release of transforming growth factor-beta after triggering by the oral tolerogen. Here, we report that in the SJL model of EAE oral administration of an autoantigen from the target tissue suppresses disease independent of whether it is or is not the inciting antigen. Thus, orally administered MBP or MBP peptides suppress proteolipid protein (PLP)-induced EAE, whereas intravenously administered MBP does not. Both oral and intravenous PLP, however, suppressed PLP disease. These findings have important implications for the use of oral tolerance as a therapeutic approach for the treatment of T cell-mediated inflammatory autoimmune diseases in man in which the inciting autoantigen is unknown or in which there is autoreactivity to multiple autoantigens in the target tissue.

Administration, Oral↗
PubMed1994

Taxol and taxotere in bladder cancer: in vitro activity and urine stability.

In this study the antimicrotubular agents taxol, taxotere, and vinblastine were compared for their ability to inhibit the clonal growth of human bladder tumor cell lines using a soft-agar clonogenic assay. The stability of taxol and taxotere was evaluated by high-performance liquid chromatography over a range of pH in human urine. Both taxol and taxotere were shown to maximally inhibit the clonal growth of human bladder cell lines within 1 h of drug incubation. The most active agent in the panel of tumor lines was taxotere, with 6 of 12 lines being sensitive to the agent at 0.01 microM and all cell lines being sensitive at 0.1 microM. Taxol was active in 1 of 12 lines at 0.01 microM and in 11 of 12 at 0.1 microM. Only 2 of 12 cell lines were sensitive to vinblastine over the 0.01- to 0.1-microM dose range. Taxol and taxotere were found to be stable in human urine for 4 h over a pH range of 5-7. At least 85% of both drugs were present during this period of drug incubation. Our findings suggest that both taxol and taxotere may be clinically useful agents for systemic and intravesical use in bladder cancer.

Antineoplastic Agents, Phytogenic↗