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Biomedical subjects

J K Rao

Publications and source records attributed to J K Rao.

At least 19 recordsLinked to original sources
PubMed1999

Use of complementary therapies for arthritis among patients of rheumatologists.

BACKGROUND: Use of complementary and alternative medicine (CAM) is common among persons with chronic conditions. OBJECTIVE: To identify correlates of and describe patients' perspective on use of CAM for rheumatologic conditions. DESIGN: Telephone survey. SETTING: Three university practices and three private rheumatology practices. PATIENTS: 232 of 428 eligible consecutive patients (54%) with scheduled appointments. MEASUREMENTS: Patients answered questions on CAM use, functional status, pain, provider satisfaction, and health services utilization. Chart reviews provided demographic information and rheumatologic diagnoses. Bivariate analyses identified correlates of four CAM outcomes (history, magnitude, and frequency of CAM use and communication about CAM use with a physician), and multiple logistic regression identified independent correlates of regular CAM use. RESULTS: Approximately two thirds of the respondents (n = 146) had used CAM. Of these 146 respondents, 82 (56%) currently used CAM and 132 (90%) regularly used CAM or had done so in the past. Fifty-five respondents (24%) had used three or more types of CAM. In multivariate analyses, persons who used CAM regularly were more likely to have osteoarthritis (odds ratio, 5.6 [95% CI, 1.9 to 16.8]), severe pain (odds ratio, 2.5 [CI, 1.4 to 4.8]), and a college degree (odds ratio, 2.6 [CI, 1.3 to 5.4]) than patients who had never used CAM. Nearly half of the respondents discussed CAM use with their physicians. The most common reasons for not disclosing CAM use were that the physician had not asked about it and that the patient forgot to tell the physician; fear of disapproval was rarely cited. Discussions about CAM use between patient and physician occurred more frequently among patients with fibromyalgia and persons who regularly used CAM or used several types of CAM. CONCLUSIONS: Patients with rheumatologic conditions frequently use CAM. Severe pain and osteoarthritis predict regular use of CAM but do not predict a greater likelihood of discussing CAM use with physicians. Routine inquiry by physicians will probably detect CAM use.

Arthralgia↗
PubMed1999

Age-related hippocampal changes in Bcl-2:Bax ratio, oxidative stress, redox-active iron and apoptosis associated with aluminum-induced neurodegeneration: increased susceptibility with aging.

We propose that aging is an important factor in the susceptibility of neurons to oxidative stress and to subsequent apoptosis. In the present report we demonstrate that aged rabbits treated intracisternally with aluminum maltolate exhibit intense intraneuronal silver positivity indicative of the formation of neurofilamentous aggregates, together with oxidative stress. These changes occur in the CA1 region of the hippocampus as well as in cerebral cortical areas. Apoptosis, measured by the TUNEL in situ technique, colocalizes with oxidative stress. Young animals treated with aluminum show few of these alterations, while age-matched controls are essentially negative. Further studies on the time course of these and related changes demonstrate that oxidative stress and redox-active iron accumulation in hippocampal neurons occur very rapidly, within a period of 3 hours, and increased in intensity at 72 hours. Changes suggestive of apoptosis are seen by 24 hours and are pronounced at 72 hours. In aged animals there is an initially intense immunopositivity at 3 hours for Bcl-2, with negative staining for Bax. By 72 hours, when apoptosis is strongly evident, Bcl-2 is negative and Bax strongly positive. In contrast to the aged rabbits, young animals treated similarly with aluminum exhibit much less oxidative stress with no apoptosis, and maintain Bcl-2 immunopositivity and negative Bax staining. Our findings strongly support the key role that oxidative damage plays in the process of neurodegeneration and in the increased vulnerability to aluminum-induced injury in the aged animal. These are novel observations which may have important implications for aiding in our understanding of the pathogenesis of neurodegeneration occurring in Alzheimer's disease.

Aging↗
PubMed1998

Crystal structure of rabbit muscle creatine kinase.

The crystal structure of rabbit muscle creatine kinase, solved at 2.35 A resolution by X-ray diffraction methods, clearly identified the active site with bound sulfates surrounded by a constellation of arginine residues. The putative binding site of creatine, which is occupied by a sulfate group in this analysis, has been tentatively identified. The dimeric interface of the enzyme is held together by a small number of hydrogen bonds.

Animals↗
PubMed1998

Limitations of the 1990 American College of Rheumatology classification criteria in the diagnosis of vasculitis.

BACKGROUND: The American College of Rheumatology (ACR) established criteria to discriminate among patients with seven types of vasculitis. Although designated as "classification criteria" for research, these criteria are often used for diagnosis. OBJECTIVE: To examine the operating characteristics of the 1990 ACR classification criteria in the diagnosis of Wegener granulomatosis, giant-cell arteritis, polyarteritis nodosa, and hypersensitivity vasculitis. DESIGN: Prospective cohort study. SETTING: University medical center and Veterans Affairs medical center. PATIENTS: 198 consecutive patients referred to rheumatologists for evaluation of possible vasculitis. MEASUREMENTS: Blinded chart audits were done to classify patients according to the 1990 ACR classification criteria for Wegener granulomatosis, polyarteritis nodosa, giant-cell arteritis, and hypersensitivity vasculitis on the basis of the patients' initial presentation. Chart audits done 2 to 8 months after baseline provided the patients' final diagnoses, which were considered the gold standard, as in the development of the ACR criteria. Test operating characteristics of the ACR classification criteria were calculated according to 2 x 2 tables for the entire cohort and for only the patients with a final diagnosis of vasculitis. RESULTS: Vasculitis was diagnosed in 51 (26%) patients. Thirty-eight (75%) of 51 patients with vasculitis and 31 (21%) of 147 patients without vasculitis met ACR criteria for one or more types of vasculitis. The positive predictive values for the four vasculitides according to ACR criteria were 17% to 29% for the entire cohort and 29% to 75% for only the patients with a final diagnosis of vasculitis. CONCLUSION: The 1990 ACR classification criteria function poorly in the diagnosis of specific vasculitides.

Diagnosis, Differential↗
PubMed1998

Using focus groups to understand arthritis patients' perceptions about unconventional therapy.

OBJECTIVE: To understand arthritis patients' use of unconventional therapies (UT). METHODS: Thirty-three rheumatoid arthritis and osteoarthritis patients followed in university clinics participated in 5 focus groups to discuss: their beliefs about arthritis and UT; UT they have used; reasons for using UT; effectiveness of UT; sources of information on UT; and communication about UT with the physician. Two investigators analyzed focus group transcripts to identify common themes. RESULTS: All patients believed arthritis to be incurable by conventional regimens or UT. Over one-half had used UT to relieve pain; cost was unimportant. Patients trusted information about UT from family, friends, and others with arthritis, but not supermarket tabloids or television commercials. Most discussed UT use with their physician, primarily to prevent interactions with prescribed treatments. Physicians' reactions ranged from ridicule to giving permission to continue using UT. CONCLUSIONS: These results provide an understanding of arthritis patients' motives for using UT and for discussing this behavior with their physician.

Adult↗
PubMed1998

Response to growth hormone in attention deficit hyperactivity disorder: effects of methylphenidate and pemoline therapy.

OBJECTIVE: To determine whether treatment of attention deficit hyperactivity disorder (ADHD) with methylphenidate hydrochloride or pemoline diminishes the response to growth hormone (GH) therapy in patients with idiopathic GH deficiency (IGHD) or idiopathic short stature (ISS). METHODS: The National Cooperative Growth Study database was used to identify patients between 3 and 20 years of age with IGHD or ISS and those within these groups who were treated with methylphenidate or pemoline for ADHD. Their growth in response to GH treatment (change in height standard deviation score [SDS]) was compared with that of patients with IGHD or ISS who were not treated for ADHD, by using a stepwise multiple regression analysis. RESULTS: In the IGHD cohort, there were 184 patients who were being treated for ADHD and 2313 who were not. In the ISS cohort there were 117 patients who were being treated for ADHD and 1283 who were not. There was a higher percentage of males being treated for ADHD in both cohorts. In the IGHD cohort, the change in height SDS was positively associated with the number of years of GH treatment, parents' heights, body mass index, and GH injection schedule, and was negatively associated with height SDS at the initiation of GH therapy, age, and maximum stimulated GH level. The use of methylphenidate or pemoline had a negative effect on the change in height SDS, but the magnitude of the effect was small. Similar effects were noted in the ISS cohort, but body mass index and the use of methylphenidate or pemoline had no effect on the change in height SDS. CONCLUSIONS: Concurrent ADHD therapy is associated with a slight decrease in the change in height SDS during GH treatment in patients with IGHD but not in those with ISS. Even in IGHD, the magnitude of the effect is small and should not deter the use of such concurrent therapy.

Attention Deficit Disorder with Hyperactivity↗
PubMed1998

Experimental aluminum encephalomyelopathy. Relationship to human neurodegenerative disease.

Alzheimer's disease has a complex pathogenesis and is a devastating neurologic disorder, predominantly of the elderly human population. Neuronal cell loss and neuritic pathology are a major neuropathologic feature of Alzheimer's disease, but there is no established mechanism to explain the degenerative process. The development of suitable animal systems would be of great value in helping to understand the basic mechanisms underlying the disease. We propose that the aluminum maltolate-treated elderly rabbit is a potentially useful animal system to model Alzheimer's disease neurofibrillary pathology. Details of such an experimental aluminum encephalopathy produced in the rabbit are discussed, along with other aspects of aluminum-induced neurodegeneration.

Aluminum↗
PubMed1997

Characteristics of persons with self-reported arthritis and other rheumatic conditions who do not see a doctor.

OBJECTIVE: To characterize persons with self-reported arthritis and other rheumatic conditions who never saw a doctor for their condition. METHODS: Comparison of 2 groups (persons who did and did not see a doctor for arthritis) identified from cross sectional data from the 1989 National Health Interview Survey (NHIS), a stratified random probability sample representative of the US civilian noninstitutionalized population. Survey respondents aged 18 years and older who answered questions on musculoskeletal conditions and self-reported arthritis (n = 2944 unweighted; 36 million weighted) were asked when they last saw a doctor for this condition. RESULTS: Of adult Americans who reported arthritis, 16.4% reported never seeing a doctor for this problem. This group was more often male and younger than those who saw a doctor for arthritis. Persons were less likely to see a doctor for arthritis if they had better self-perceived health, fewer activity or work limitations due to arthritis, no health insurance, and if they were not overweight. Of those who reported never visiting a doctor for arthritis, 72.8% reported one or more doctor visits within the preceding 12 months. Weighted estimates indicate that nearly 6 million Americans with self-reported arthritis never see a doctor for their condition, including 191,000 with activity limitations due to arthritis. About 4.3 million of the 6 million people with arthritis reported at least one doctor visit within the previous 12 months. CONCLUSION: A "better" health profile and lack of health insurance may explain why some people do not see a doctor for arthritis. A substantial number, however, have both severe disease as well as health insurance that covers doctor visits for other medical problems. These visits represent missed opportunities for early diagnosis and effective medical and behavioral intervention.

Adult↗
PubMed1996

The oligomerization domain of p53: crystal structure of the trigonal form.

The structure of the oligomerization domain of the p53 tumor suppressor protein was determined in the trigonal crystal form, using a refined NMR structure as a model. A synthetic peptide comprising residues 319-360 of human p53 crystallized in the space group P3(1)21. There is one biologically relevant tetrameric domain in the crystallographic asymmetric unit. The structure was refined jointly with NMR data, only the third such case (the previous examples being IL-1beta (Shaanan, B., Gronenborn, A.M., Cohen, G.H., Gilliland, G.L., Veerapandian, B., Davies, D.R. and Clore, G.M. (1992) Science 257, 961-964 [1]) and BPTI (Schiffer, C., Huber, R., Wuthrich, K. and Van Gunsteren, W.F. (1994) J. Mol. Biol. 241, 588-599 [21)), to 2.5 A resolution with an R factor of 0.207. The distribution of tumor-derived mutations in the oligomerization region together with structural and biological data suggest a strategy for the design of antitumor therapeutics.

Biopolymers↗
PubMed1996

Invasion of human glioma: role of extracellular matrix proteins.

The invasion of glioma into normal brain tissue is a major challenge to clinical intervention because these tumors often highly infiltrate the surrounding brain tissue. Total surgical resection of gliomas is impossible, and recurrence of tumor growth is a common phenomenon; patients have a mean survival time of 8-12 months. Although in recent years substantial progress has been made toward understanding the invasive behavior of gliomas in vitro and in vivo, the factors responsible for the extensive infiltration are still poorly documented. This review focuses on recent research concerning the invasion of gliomas, as well as the extracellular matrix components, and the proteolytic enzymes involved. A better understanding of cell-matrix interactions will help in developing therapeutic strategies to decrease the invasion of gliomas.

Brain Neoplasms↗
PubMed1996

New insights into the epidemiology of systemic vasculitis.

Because of the relative rarity of the conditions, epidemiologic investigation of systemic vasculitis is a challenging prospect. Previous work in this area has been primarily in the form of descriptive studies and therapeutic trials, which have increased awareness of these syndromes among clinicians. However, compared with other diseases, little is known about the epidemiology of the systemic vasculitides. Although significant progress has been made during the past year to estimate incidence and prevalence rates of disease, particularly for giant cell arteritis and Kawasaki disease, further studies are needed to determine risk factors for initial expression and relapses of vasculitis, biologic markers of disease progression, comorbidities, long-term outcomes, and cost of care and disability.

Humans↗
PubMed1995

The role of antineutrophil cytoplasmic antibody (c-ANCA) testing in the diagnosis of Wegener granulomatosis. A literature review and meta-analysis.

PURPOSE: To summarize the literature on the clinical utility of antineutrophil cytoplasmic antibody (c-ANCA) as a diagnostic marker for Wegener granulomatosis. DATA SOURCES: A structured literature search was done using MEDLINE; this search, combined with a manual search, yielded 747 articles for potential inclusion. These articles passed through a 4-stage review. Studies were included if they had a specified reference standard and a systematic method of patient selection and if a 2 x 2 contingency table could be constructed from their results. Fifteen articles met these criteria. DATA EXTRACTION: 3 physicians reviewed all selected articles. Detailed data abstraction was done, and the quality of the study methods was assessed. Items abstracted included the method of patient selection, the study design, the reference standard, the c-ANCA testing technique, disease activity, and the test results. Disagreements among reviewers were resolved by consensus. Contingency tables were used to calculate the operating characteristics for Wegener granulomatosis overall and for active and inactive Wegener granulomatosis. RESULTS: The sensitivities of c-ANCA testing for overall Wegener granulomatosis ranged from 34% to 92%, and the specificities ranged from 88% to 100%. The pooled sensitivity was 66% (95% CI, 57% to 74%), and the pooled specificity was 98% (CI, 96% to 99.5%). Four articles provided data on disease activity. For active disease, the pooled sensitivity was 91% (CI, 87% to 95%), and the pooled specificity was 99% (CI, 97% to 99.9%). For inactive disease, the pooled sensitivity and specificity were 63% and 99.5%, respectively. CONCLUSIONS: Although c-ANCA test results may serve clinicians as adjunct evidence for the diagnosis of Wegener granulomatosis, these results must be viewed in the context of the patient's clinical picture and disease activity and the prevalence of Wegener granulomatosis in the clinical setting in which the patient is seen.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1995

A prospective study of antineutrophil cytoplasmic antibody (c-ANCA) and clinical criteria in diagnosing Wegener's granulomatosis.

Antineutrophil cytoplasmic antibody (c-ANCA) has a reported sensitivity and specificity greater than 90% for active Wegener's granulomatosis in selected patients with previously-defined disease. Because of these reports, some clinicians believe that a positive c-ANCA result provides strong circumstantial evidence for the diagnosis of Wegener's granulomatosis in patients with compatible clinical symptoms. However, this approach has not been examined prospectively. We prospectively studied 346 consecutive patients suspected of having vasculitis; those with previously established Wegener's granulomatosis (n = 29) or receiving immunosuppressives other than corticosteroids (n = 65) at baseline were excluded. Measures included a baseline c-ANCA, blinded chart reviews to record symptoms, physical findings, and corticosteroid use at baseline, and 2 to 8 months later to record final diagnoses and biopsy results. Wegener's granulomatosis was defined using the 1990 American College of Rheumatology (ACR) criteria, which does not require a biopsy. Follow-up information was available for 212 (84%) of the 252 patients eligible for this study (no corticosteroids: n = 174; corticosteroids: n = 78). 25 patients with compatible symptoms were classified with Wegener's granulomatosis by ACR criteria; only 6 of the 25 had biopsy-proven disease. 14 of these 212 patients had positive c-ANCA results. The overall sensitivity and specificity of c-ANCA for ACR-defined Wegener's granulomatosis were 28% (95% CI, 10%-46%) and 96% (93%-99%) respectively. The positive and negative predictive values were 0.50 and 0.91. The specificity remained greater than 90% regardless of baseline corticosteroid use or disease activity; however, the sensitivity and positive predictive value remained poor. For Wegener's granulomatosis defined by biopsy criteria and compatible clinical symptoms, the sensitivity was 83% (53%-100%); however, the positive predictive value was 36%. These results raise serious questions about the use of positive c-ANCA tests in diagnosing Wegener's granulomatosis in patients with clinical symptoms alone.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1995

Systems for data analysis.

A system for data analysis is the end product of study planning, form design, data entry, data verification, and statistical analysis. This article reviews these steps and considers the fundamental choices in software for data entry and analysis. The appendix includes a listing of general and specialized software for data management and statistical analysis.

Data Interpretation, Statistical↗
PubMed1994

Implantable controlled delivery systems for proteins based on collagen--pHEMA hydrogels.

Co-polymeric hydrogels of collagen and poly(hydroxyethyl methacrylate) (pHEMA) were prepared using an ammonium persulphate-sodium metabisulphite redox initiation technique. Fluorescein isothiocyanate (FITC)-labelled bovine serum albumin (BSA) was entrapped into these hydrogels. These gels were modified differently by external cross-linking and made highly porous by incorporation of ethylene glycol. The morphological characteristics of the gels containing FITC-BSA before and after release were studied. The in vitro release of FITC-labelled BSA was studied in phosphate buffer, pH 7.4, at 37 degrees C. The results clearly indicated that collagen-pHEMA hydrogels release FITC-BSA in a zero-order fashion. In the case of uncross-linked hydrogels, the release of FITC-BSA was about 81% within 8 d, compared to 49% for the same period in the case of cross-linked hydrogels. It was also observed that in the case of porous hydrogels the release was very fast (19% in the first hour) and lasted for about 12 h, releasing 76% of FITC-BSA. These results clearly indicated that collagen-pHEMA hydrogels released BSA in a zero-order fashion and that the release rate can be programmed by appropriate modification of the hydrogel matrices.

Animals↗
PubMed1994

Controlled release systems for proteins based on gelatin microspheres.

The preparation and characterization of biodegradable gelatin microspheres for the controlled release of peptides and proteins has been investigated. Bovine serum albumin (BSA) was chosen for incorporation into the gelatin microspheres and the spheres were characterized for the in vitro release of BSA and other properties. BSA was labelled with fluorescein isothiocyanate (FITC) for easy analysis. FITC-BSA was entrapped into the gelatin microspheres using a polymer dispersion technique developed in our earlier studies. The morphological characteristics of microspheres were analysed by optical and scanning electron microscopy (SEM). The optical and SEM photographs of FITC-BSA microspheres showed the solid spherical nature of the spheres. The entrapment efficiency of FITC-BSA was about 62%. The in vitro release pattern of FITC-BSA showed that 51% of the entrapped drug was released during the first day and the release followed approximate zero order kinetics from day 2 onwards. The total release of FITC-BSA lasted for about 8 days. SDS-PAGE analysis revealed that BSA was not degraded by this preparation of microspheres.

Biodegradation, Environmental↗
PubMed1993

A left-handed crossover involved in amidohydrolase catalysis. Crystal structure of Erwinia chrysanthemi L-asparaginase with bound L-aspartate.

The crystal structure of L-asparaginase from Erwinia chrysanthemi in the presence and absence of L-aspartate was determined at 1.8 A resolution. Conserved residues in a left-handed crossover (a rare occurrence in protein structures) link pairs of dimers into the catalytically active tetrameric form of the enzyme. The structure of ErA containing bound aspartic acid shows that this unusual strand connectivity is an essential part of the active site architecture, responsible for releasing the product of the enzymatic hydrolysis. The orientation of the bound aspartate indicates for the first time a threonine residue as a catalytic nucleophile.

Amidohydrolases↗