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Biomedical subjects

J Santoro

Publications and source records attributed to J Santoro.

At least 19 recordsLinked to original sources
PubMed2004

The validity and accuracy of the Work Productivity and Activity Impairment questionnaire--irritable bowel syndrome version (WPAI:IBS).

BACKGROUND: Irritable bowel syndrome is a common chronic functional gastrointestinal disorder characterized by recurrent abdominal pain and discomfort associated with alterations in bowel habit. Irritable bowel syndrome affects patients' quality of life and increases productivity loss. AIM: To assess validity and accuracy of the Work Productivity and Activity Impairment questionnaire in irritable bowel syndrome as a tool for quantifying the effects of irritable bowel syndrome on productivity and daily activities. METHODS: Validity and accuracy were evaluated in 135 irritable bowel syndrome patients relative to three measures of irritable bowel syndrome disease severity; a debriefing questionnaire; retrospective diary; Work Limitations Questionnaire, and an activity impairment measure (Dimensions of Daily Activities). RESULTS: Symptom severity scores, diary scores, Work Limitations Questionnaire and Dimensions of Daily Activities were significant predictors of work productivity and activity impairment questionnaire in irritable bowel syndrome measures of work time missed, and work and activity productivity loss (P = 0.04 to < 0.0001). Impairment due to irritable bowel syndrome was estimated to be 2.9-4.3% for work time missed and 22-32% for impairment at work, the equivalent of 9.7 -14 h lost productivity per week. Activity impairment was 24-41%. CONCLUSIONS: Discriminative validity of the Work Productivity and Activity Impairment questionnaire in irritable bowel syndrome was established, making it the only validated tool for measuring the relative differences between disease severity groups and quantifying work productivity loss and activity impairment in irritable bowel syndrome patients.

Absenteeism↗
PubMed2002

Solution structure of allergenic 2 S albumins.

The NMR solution structures at different levels of refinement of three different 2 S albumin seed proteins, the recombinant pronapin precursor from Brassica napus, the recombinant RicC3 from Ricinus communis and the methionine-rich protein from sunflower ( Helianthus annuus ), are described. The resulting common structure consists of a bundle of five alpha-helices, folded in a right-handed superhelix. The structure is very similar to that of other plant proteins: the hydrophobic protein from soybean, non-specific lipid transfer proteins and amylase/trypsin inhibitors. Analogies and differences in the structures of these families, as well as their possible relationship to allergenicity, are discussed.

2S Albumins, Plant↗
PubMed2001

Solution structure and dynamics of ribonuclease Sa.

We have used NMR methods to characterize the structure and dynamics of ribonuclease Sa in solution. The solution structure of RNase Sa was obtained using the distance constraints provided by 2,276 NOEs and the C6-C96 disulfide bond. The 40 resulting structures are well determined; their mean pairwise RMSD is 0.76 A (backbone) and 1.26 A (heavy atoms). The solution structures are similar to previously determined crystal structures, especially in the secondary structure, but exhibit new features: the loop composed of Pro 45 to Ser 48 adopts distinct conformations and the rings of tyrosines 51, 52, and 55 have reduced flipping rates. Amide protons with greatly reduced exchange rates are found predominantly in interior beta-strands and the alpha-helix, but also in the external 3/10 helix and edge beta-strand linked by the disulfide bond. Analysis of (15)N relaxation experiments (R1, R2, and NOE) at 600 MHz revealed five segments, consisting of residues 1-5, 28-31, 46-50, 60-65, 74-77, retaining flexibility in solution. The change in conformation entropy for RNase SA folding is smaller than previously believed, since the native protein is more flexible in solution than in a crystal.

Entropy↗
PubMed2001

Use of antibacterial agents in renal failure.

This article reviews the pharmacokinetics of antibacterial agents in patients with normal and decreased renal function. The concepts of volume and distribution, rate of elimination, loading and maintenance doses, and therapeutic drug monitoring are delineated. Special reference is made to the intermittent dosing of cefazolin with hemodialysis. Newer, as well as traditional methods of extracorporeal circulation and the resultant changes in antibacterial agent pharmacodynamics are discussed.

Anti-Infective Agents↗
PubMed2000

The highly refined solution structure of the cytotoxic ribonuclease alpha-sarcin reveals the structural requirements for substrate recognition and ribonucleolytic activity.

alpha-Sarcin selectively cleaves a single phosphodiester bond in a universally conserved sequence of the major rRNA, that inactivates the ribosome. The elucidation of the three-dimensional solution structure of this 150 residue enzyme is a crucial step towards understanding alpha-sarcin's conformational stability, ribonucleolytic activity, and its exceptionally high level of specificity. Here, the solution structure has been determined on the basis of 2658 conformationally relevant distances restraints (including stereoespecific assignments) and 119 torsional angular restraints, by nuclear magnetic resonance spectroscopy methods. A total of 60 converged structures have been computed using the program DYANA. The 47 best DYANA structures, following restrained energy minimization by GROMOS, represent the solution structure of alpha-sarcin. The resulting average pairwise root-mean-square-deviation is 0.86 A for backbone atoms and 1.47 A for all heavy atoms. When the more variable regions are excluded from the analysis, the pairwise root-mean-square deviation drops to 0.50 A and 1.00 A, for backbone and heavy atoms, respectively. The alpha-sarcin structure is similar to that reported for restrictocin, although some differences are clearly evident, especially in the loop regions. The average rmsd between the structurally aligned backbones of the 47 final alpha-sarcin structures and the crystal structure of restrictocin is 1.46 A. On the basis of a docking model constructed with alpha-sarcin solution structure and the crystal structure of a 29-nt RNA containing the sarcin/ricin domain, the regions in the protein that could interact specifically with the substrate have been identified. The structural elements that account for the specificity of RNA recognition are located in two separate regions of the protein. One is composed by residues 51 to 55 and loop 5, and the other region, located more than 11 A away in the structure, is the positively charged segment formed by residues 110 to 114.

Allergens↗
PubMed2000

The Caregiver Activity Survey (CAS): longitudinal validation of an instrument that measures time spent caregiving for individuals with Alzheimer's disease.

Family members incur substantial financial costs during the course of caring for an individual with Alzheimer's disease. Much of this cost is associated with time spent in caregiving tasks, including supervision and communication with the patient, and assisting with activities of daily living. We have previously reported on the cross sectional reliability and validity of a scale that measures time spent caregiving, the Caregiver Activity Survey (CAS). This study extends our results to a longitudinal study of the validity of the instrument. Forty-four outpatients with Alzheimer's disease who lived with a primary caregiver were followed over a period of 1 year 6 months. At six month intervals, the patients were administered the Mini Mental State Exam (MMSE), Alzheimer's Disease Assessment Scale (ADAS), and the Physical Self Maintenance Scale (PSMS). Caregivers completed the CAS. Over time, the CAS correlated significantly with the MMSE (r=-0.58, p=0.000), ADAS cognitive subscale (r=0.56, p=0. 000) and PSMS (r=0.49, p=0.000). As patients declined, caregivers spent less time communicating with and more time supervising the patient. Excluding the communication item, time spent caregiving increased significantly over time. This prospective study longitudinally validates the CAS with Alzheimer's patients.

Activities of Daily Living↗
PubMed2000

Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis.

BACKGROUND: Functional gastrointestinal disorders are common, accounting for up to 50% of gastroenterology referrals, and several randomized controlled trials have evaluated antidepressant therapy for their treatment. METHODS: We performed a meta-analysis of published, English-language, randomized clinical trials on the use of antidepressants for the treatment of patients with functional gastrointestinal disorders. RESULTS: Twelve randomized placebo-controlled trials of antidepressant treatment of functional gastrointestinal disorders were identified. One was excluded for using a combination of a tricyclic and neuroleptic agent. The medications included tricyclic antidepressants (amitriptyline [n = 3], clomipramine [n = 1], desipramine [n = 2], doxepin [n = 1], and trimipramine [n = 2]), and the antiserotonin agent, mianserin (n = 2). In addition, one trial compared two different antidepressants (mianserin and clomipramine) with placebo. Data were abstracted for the dichotomous outcome of symptom improvement in seven studies, and for the continuous variable of pain score in eight studies. The summary odds ratio for improvement with antidepressant therapy was 4.2 (95% confidence interval [CI]: 2.3 to 7.9), and the average standardized mean improvement in pain was equal to 0.9 SD units (95% CI: 0.6 to 1.2 SD units). On average 3.2 patients needed to be treated (95% CI: 2.1 to 6.5 patients) to improve 1 patient's symptom. CONCLUSION: Treatment of functional gastrointestinal disorders with antidepressants appears to be effective. Whether this improvement is independent of an effect of treatment on depression needs further evaluation.

Adult↗
PubMed2000

Use of antibacterial agents in renal failure.

This article provides information on the pharmacokinetics of antibacterial agents in patients with normal renal function and those with impaired renal function. Specific discussion includes the use of serum levels, dosage adjustments in dialysis, new strategies for cefazolin dosages in dialysis patients, and antibiotic toxicity in renal failure, and tabular data is presented for determining appropriate dosages for varying degrees of renal failure.

Anti-Bacterial Agents↗
PubMed2000

Treatment of fibromyalgia with antidepressants: a meta-analysis.

BACKGROUND: Fibromyalgia is a common, poorly understood musculoskeletal pain syndrome with limited therapeutic options. OBJECTIVE: To systematically review the efficacy of antidepressants in the treatment of fibromyalgia and examine whether this effect was independent of depression. DESIGN: Meta-analysis of English-language, randomized, placebo-controlled trials. Studies were obtained from searching MEDLINE, EMBASE, and PSYCLIT (1966-1999), the Cochrane Library, unpublished literature, and bibliographies. We performed independent duplicate review of each study for both inclusion and data extraction. MAIN RESULTS: Sixteen randomized, placebo-controlled trials were identified, of which 13 were appropriate for data extraction. There were 3 classes of antidepressants evaluated: tricyclics (9 trials), selective serotonin reuptake inhibitors (3 trials), and S-adenosylmethionine (2 trials). Overall, the quality of the studies was good (mean score 5.6, scale 0-8). The odds ratio for improvement with therapy was 4.2 (95% confidence interval [95% CI], 2.6 to 6.8). The pooled risk difference for these studies was 0.25 (95% CI, 0.16 to 0.34), which calculates to 4 (95% CI, 2.9 to 6.3) individuals needing treatment for 1 patient to experience symptom improvement. When the effect on individual symptoms was combined, antidepressants improved sleep, fatigue, pain, and well-being, but not trigger points. In the 5 studies where there was adequate assessment for an effect independent of depression, only 1 study found a correlation between symptom improvement and depression scores. Outcomes were not affected by class of agent or quality score using meta-regression. CONCLUSION: Antidepressants are efficacious in treating many of the symptoms of fibromyalgia. Patients were more than 4 times as likely to report overall improvement, and reported moderate reductions in individual symptoms, particularly pain. Whether this effect is independent of depression needs further study.

Adult↗
PubMed1999

De novo design of a monomeric three-stranded antiparallel beta-sheet.

Here we describe the NMR conformational study of a 20-residue linear peptide designed to fold into a monomeric three-stranded antiparallel beta-sheet in aqueous solution. Experimental and statistical data on amino acid beta-turn and beta-sheet propensities, cross-strand side-chain interactions, solubility criteria, and our previous experience with beta-hairpins were considered for a rational selection of the peptide sequence. Sedimentation equilibrium measurements and NMR dilution experiments provide evidence that the peptide is monomeric. Analysis of 1H and 13C-NMR parameters of the peptide, in particular NOEs and chemical shifts, and comparison with data obtained for two 12-residue peptides encompassing the N- and C-segments of the designed sequence indicates that the 20-residue peptide folds into the expected conformation. Assuming a two-state model, the exchange kinetics between the beta-sheet and the unfolded peptide molecules is in a suitable range to estimate the folding rate on the basis of the NMR linewidths of several resonances. The time constant for the coil-beta-sheet transition is of the order of several microseconds in the designed peptide. Future designs based on this peptide system are expected to contribute greatly to our knowledge of the many factors involved in beta-sheet formation and stability.

Amino Acids↗
PubMed1999

CSF beta-amyloid, cognition, and APOE genotype in Alzheimer's disease.

OBJECTIVES: We examined the relationship between CSF amyloid beta peptide (A beta) concentration and AD severity in 31 probable AD patients and explored whether APOE genotype modifies this relationship. BACKGROUND: A beta deposition in AD brains has been correlated with disease severity and with APOE-epsilon4 allele frequency. Few studies have examined the effects of APOE genotype on the relationship between CSF A beta and disease severity in an antemortem sample. METHODS: Patients carried the clinical diagnosis of probable AD and did not have serious medical illness, current or past diagnosis of mood disorder, schizophrenia or alcoholism, or current psychotic features. The Mini-Mental State Examination (MMSE) was administered to the patient within 3 months of CSF collection. CSF was analyzed for A beta1-40 and A beta1-42 by sandwich ELISAs, and APOE genotype was determined by PCR run from blood. Correlations were performed between MMSE score and A beta1-40 and A beta1-42 concentrations while controlling for potential confounding variables. RESULTS: CSF measures of A beta1-40 and A beta1-42 concentrations were correlated with each other (r = 0.56, df = 28, p < 0.01). CSF A beta1-40 and A beta1-42 concentrations were positively correlated with MMSE score. The negative association between CSF A beta measures and disease severity remained significant after controlling for age (A beta1-40 and MMSE score: r = 0.46, df = 28, p = 0.01; A beta1-42 and MMSE score: r = 0.35, df = 28, p = 0.05). Among the APOE-epsilon3/3 homozygotes there was a significant positive correlation only between A beta1-42 and MMSE score (A beta1-42, r = 0.94, p = 0.02; A beta1-40, r = 0.79, p = 0.11). CONCLUSIONS: We hypothesize that an increased deposition of A beta in plaques results in decreased CSF A beta concentration. The stronger relationship between MMSE score and CSF A beta, specifically in APOE-epsilon3/3 homozygotes, suggests that patients with APOE-epsilon3/3 genotype may have different pathogenic mechanisms than the other genotypes for A beta deposition or clearance.

Aged↗
PubMed1999

Antidepressant therapy for unexplained symptoms and symptom syndromes.

OBJECTIVE: To determine the efficacy of antidepressant therapy for unexplained symptoms or symptom syndromes. SEARCH STRATEGIES: We identified original studies through searching MEDLINE, EMBASE, PsycLIT, the Federal Research in Progress database, and The Cochrane Library. We also searched the bibliographies of primary and review articles for additional studies. SELECTION CRITERIA: We excluded trials of patients with neuropathic, oncologic, or degenerative joint pain. Independent duplicate review of 392 articles identified 94 relevant reports of randomized trials involving 6595 patients across 6 symptom syndromes. Independent duplicate assessment was made for inclusion and data abstraction. Meta-analysis was performed on extractable placebo-controlled data. MAIN RESULTS: Of 94 included trials, most studied either tricyclic antidepressants, antiserotonin antidepressants, selective serotonin reuptake inhibitors (SSRIs), or multiple agents for the treatment of the following syndromes: headache (50), fibromyalgia (18), functional gastrointestinal syndromes (13), idiopathic pain (11), tinnitus (2), and chronic fatigue (2). The quality of the studies was fair (mean score = 4.8 on a scale of 0 to 8). A majority of the studies (69%) demonstrated benefit for at least one outcome measure. Symptom improvement typically did not correlate with depression response in the few studies where it was assessed. Meta-analysis of all extractable data showed a substantial benefit from antidepressants: For the dichotomous outcome of improvement, the odds ratio was 3.4 (95% confidence interval [CI], 2.6 - 4.5), and for continuous outcomes, the standardized mean difference was 0.87 (95% CI, 0.59-1.14). The absolute percentage difference in improvement between the antidepressant and placebo arms was 32%, yielding a number needed to treat of 3 to improve one person's symptoms. Meta-regression indicated no differential effect across the classes of antidepressants; however, onbivariate tally tricyclic studies were associated with a greater likelihood of efficacy than SSRI studies (P = .02). CONCLUSIONS: Antidepressants can be effective for various physical symptoms and symptom syndromes. The relation of outcome to depression and the efficacy of SSRIs needs further study.

Adult↗