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H J Williams

Publications and source records attributed to H J Williams.

At least 19 recordsLinked to original sources
PubMed1996

NMR and molecular modeling study of the conformations of taxol 2'-acetate in chloroform and aqueous dimethyl sulfoxide solutions.

Taxol 2'-acetate, an analog of the antitumor drug taxol, displays no significant in vitro microtubule polymerization activity, thus underscoring the importance of a free 2'-OH group to the biological activity of taxol. Previous work had suggested that the inactivity of taxol 2'-acetate is not due to steric interference by the acetyl group. The present study examined the conformations of taxol 2'-acetate in deuteriochloroform and (2)H2O-deuteriodimethyl sulfoxide solutions and found them to be essentially the same as the respective conformations adopted by taxol itself. Thus, neither destabilization of an active taxol conformation by the acetyl group nor the formation of an important taxol conformation determining role for the 2'-OH group appears likely. The implication of these findings is that the taxol 2'-OH group interacts directly with a protein residue in the taxol-microtubule complex, perhaps as a hydrogen bond donor.

Acetates↗
PubMed1996

Early undifferentiated connective tissue disease. IV.Musculoskeletal manifestations in a large cohort of patients with undifferentiated connective tissue diseases compared with cohorts of patients with well-established connective tissue diseases: followup analyses in patients with unexplained polyarthritis and patients with rheumatoid arthritis at baseline.

OBJECTIVES: To examine the musculoskeletal manifestations in a large cohort of patients (n = 410) diagnosed with either a well-established connective tissue disease (CTD) (n = 197) or an early undifferentiated CTD (n = 213) with a symptom duration of <1 year. This study was aimed at determining the predictive value of demographic, clinical, and laboratory features on outcome in patients with unexplained polyarthritis (UPA) (from the early undifferentiated CTD cohort; n = 67) or rheumatoid arthritis (RA) (from the well-established CTD cohort; n = 57), over a 5-year followup period. METHODS: Patients from both cohorts were assessed at years 1, 3, and 5. At the study visits, clinical data were collected in a standardized manner, and sera were obtained and stored. A priori criteria were established for patient ascertainment and diagnosis over the duration of the study. Standard statistics were used for comparisons of baseline characteristics in patients diagnosed as having systemic lupus erythematosus, RA, undifferentiated CTD, and UPA at entry into the cohorts. Baseline features in patients with UPA were examined according to the different subsequent outcomes (RA, CTD, or undifferentiated CTD, remission [nonpersistent], or persistent or active UPA). Baseline features in patients with RA whose disease remained active versus those in whom remission was attained were also examined. Two multivariable analyses, classification trees and polychotomous logistic regression, were performed to predict disease outcomes over time. RESULTS: The overall rate of ascertainment for the 410 patients ranged from 90 % at year 1 to 71 % at year 5. Patients with established CTDs showed a tendency for more stable diagnoses than those with early undifferentiated CTDs (90-100% versus 45-70%). Consistent baseline predictors of persistent active disease among patients with RA, in both univariate and multivariable analyses, were higher joint counts for pain and tenderness and higher erythrocyte sedimentation rate (ESR). In approximately 20% of patients who were classified as having RA when they originally entered the cohort, the disease was in remission at 5 years. Twenty percent of the patients originally classified as having UPA developed RA over the duration of the study. These patients tended to be older and to have swelling of small joints at baseline. However, a consistent pattern of predictive variables could not be identified in the multivariable analyses, other than at year 1 (higher small joint counts for swelling and higher ESR). CONCLUSION: Baseline features (joint counts, and ESR) among RA patients were variously predictive of persistently active disease at years 1-5. Consistent baseline predictors of outcome among patients with UPA only emerged at year 1. Remission occurred in approximately 20% of RA patients, whereas a similar percentage of patients with UPA developed RA. These findings have implications with regard to treatment decisions in patients with early RA and/or UPA.

Adult↗
PubMed1996

Systemic lupus erythematosus: predictors of its occurrence among a cohort of patients with early undifferentiated connective tissue disease: multivariate analyses and identification of risk factors.

OBJECTIVE: To determine predictors of the occurrence of systemic lupus erythematosus (SLE) in patients with early (< or = 1 yr) undifferentiated connective tissue disease (CTD). METHODS: Analysis of a cohort of 213 patients with early undifferentiated CTD at entry, followed for 5 yrs at 11 tertiary centers. Baseline demographic, clinical, and laboratory data were compared using univariate and Cox multivariate regression analyses to identify possible predictive features for the subsequent occurrence of SLE. RESULTS: 143 of 213 patients had ascertainable clinical status at 5 yrs. By univariate analyses those who evolved to SLE (13%) were more likely to be younger, African-American, and to have alopecia, serositis, discoid lupus, positive Coombs' test, positive anti-dsDNA and anti-Sm antibodies, positive ANA (homogeneous pattern), and/or a false positive test for syphilis. Discoid lupus (relative risk = 15.8), serositis (4.1), ANA-homogeneous (4.8), and anti-Sm positivity (28.2) were retained as predictors of the occurrence of SLE in the Cox regression model. CONCLUSION: Some clinical and laboratory features in patients with early undifferentiated CTD can predict the subsequent occurrence of SLE.

Adult↗
PubMed1996

Hereditary osteoarthritis with mild spondyloepiphyseal dysplasia--are there "hot spots" on COL2A1?

OBJECTIVE: To define the genetic basis of a family with an autosomal, dominantly inherited form of spondyloepiphyseal dysplasia (SED) associated with tall stature. METHODS: A 6 generation family with early onset osteoarthritis (OA) associated with mild SED was studied. 14 individuals were examined clinically and radiologically, and DNA analysis was performed on 5. As the clinical pattern of joint involvement and tall stature of affected individuals resembled a family recently reported with an exon 11 mutation in COL2A1, this same mutation was specifically sought. In 2 clinically affected and 3 unaffected family members, exon 11 was amplified by polymerase chain reaction (PCR) followed by restriction enzyme digestion with Asp H1, the enzyme recognition sequence of which is altered by the mutation. The PCR product containing exon 11 was then directly sequenced. RESULTS: OA with widespread involvement of peripheral joints, in addition to spondylodysplasia, was seen in 14 members of the kindred. Affected family members had brachydactyly and were of average to above average height. Asp H1 digestion of the PCR product containing exon 11 in those with clinical disease was consistent with the presence of a mutation. Direct sequencing of this PCR product conclusively showed that a single base substitution was present in those with clinical disease, resulting in an arginine 75-cysteine (Arg75-Cys) mutation. CONCLUSION: We describe a 3rd family with an Arg75-Cys mutation with precocious generalized OA and mild SED. This finding supports the concept of mutational hot spots on COL2A1 related to the hypermutability of the cytosine-guanine doublet.

Adolescent↗
PubMed1995

Reliability and validity of the CSSRD functional assessment survey in rheumatoid arthritis. Cooperative Systematic Studies of Rheumatic Diseases.

OBJECTIVE: To demonstrate the reliability and validity characteristics of a fast, intensively focused functional assessment questionnaire that has been used in rheumatoid arthritis clinical trials by the Cooperative Systematic Studies of Rheumatic Diseases group (CSSRD). METHODS: Data from three double-blind, controlled clinical trials by CSSRD were used to examine the properties of the Functional Assessment Survey as a measure of physiologic function. RESULTS: The Functional Assessment Survey has reasonable test-retest reliability and convergent validity with the Steinbrocker et al. functional class. It demonstrated appropriate divergent validity with other clinical measures of response, as well as discriminant validity. CONCLUSIONS: The CSSRD Functional Assessment Survey is brief, intensive, and focused. Reliability and validity characteristics have been documented.

Activities of Daily Living↗
PubMed1995

Subdural fluid collections: an unusual manifestation of CNS disease in a connective tissue disorder.

We describe a case of autoimmune cerebritis/meningitis presenting as altered mental status that was associated with subdural fluid collections in a connective tissue disorder patient. The fluid collections cleared following high dose corticosteroid therapy and the patient's clinical status improved promptly. Subdural fluid collections have not been previously reported as a manifestation of autoimmune CNS disease.

Adult↗
PubMed1995

Diversity in cyclic sesquiterpene production by Gossypium hirsutum.

Major sesquiterpene components of oil of Texas Race Stock 810 of Gossypium hirsutum were alpha- and beta-selinene. This is the seventh cyclic terpene type found to date in this genus. Both alpha- and beta-selinene, along with aromadendrene, were found but only as minor components of extracts of several domestic cultivars of G. hirsutum.

Gossypium↗
PubMed1995

Rheumatoid arthritis: status of drug therapies.

This article describes the current drug therapies used to manage rheumatoid arthritis (RA). A brief description of the pathology, pathogenesis, and clinical features of RA is presented. The purpose of the article is to increase an awareness among physical therapists regarding the medications their patients might be taking and how these agents might influence the outcome of physical therapy intervention. The general approach to prescribing medication is presented according to the status of the disease. The attributes of nonsteroidal antiinflammatory drugs, corticosteroids, slow-acting antirheumatic drugs, and cytotoxic and experimental drugs used in RA are described. Given the potential benefits, side effects, and adverse reactions of these potentially powerful medications, it is important for the physical therapist to monitor closely what is happening to the patient with respect to the use or nonuse of the medication.

Adrenal Cortex Hormones↗
PubMed1995

Life's lessons.

Explore the source record for details and available documents.

Humans↗
PubMed1995

Overview of combination second-line or disease-modifying antirheumatic drug therapy in rheumatoid arthritis.

This article discusses the use of combinations of disease-modifying antirheumatic drugs (DMARDs) in the treatment of rheumatoid arthritis (RA). Patients with RA have a disease that can be disabling and life threatening and current therapies do not prevent these complications. The need for more aggressive therapy is apparent. The rationale for combinations of DMARDs is explored and the efficacy and safety of reported combinations is summarized. The variables to be reviewed in selecting a combination of DMARDs are examined. Newer approaches employing multiple DMARDs will be considered.

Antirheumatic Agents↗
PubMed1994

Clinical correlations of osteoarthritis associated with a single-base mutation (arginine519 to cysteine) in type II procollagen gene. A newly defined pathogenesis.

OBJECTIVE: To investigate the occurrence and clinical correlation of the arg519-to-cys mutation in the type II procollagen gene in patients with osteoarthritis (OA). METHODS: Sixty-six subjects from 7 families with a strong family history of generalized OA and 13 patients with erosive OA were evaluated clinically and radiologically. Blood samples from 58 subjects in the familial OA group and from all 13 patients with erosive OA were obtained for DNA analysis. Exon 31 of COL2A1, which spans residue 519, was amplified by polymerase chain reaction. RESULTS: The arg519-to-cys mutation was detected in 2 of the 7 families with generalized OA. In these 2 families, the mutation was present in the 2 probands and in 19 other clinically affected family members, as well as in 3 (so-far) clinically unaffected family members (ages 25, 14, and 11 years). It was absent in 18 clinically unaffected members tested. The mutation was associated with a distinctive pattern of early-onset, aggressive, generalized OA with a mild spinal chondrodysplasia. Inheritance was autosomal dominant. No mutation was found in any of the patients with erosive OA. CONCLUSION: The arg519-to-cys mutation defines a new pathogenic factor in generalized OA with characteristic clinical and radiologic features. The demonstration of a mutation in 3 of 8 families with OA studied thus far suggests a significant incidence of genetically related clinical OA.

Adolescent↗
PubMed1994

Methotrexate for rheumatoid arthritis. Suggested guidelines for monitoring liver toxicity. American College of Rheumatology.

Methotrexate (MTX) has become an important drug in the treatment of rheumatoid arthritis (RA). The American College of Rheumatology convened a committee to assess the risks of development of clinically significant liver disease (CSLD) during MTX treatment, to evaluate the risk and role of surveillance liver biopsies, and to provide recommendations about monitoring patients for liver toxicity. The committee recommends obtaining liver blood tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, albumin, bilirubin), hepatitis B and C serologic studies, and other standard tests including complete blood cell count and serum creatinine tests prior to starting treatment with MTX. A pretreatment liver biopsy should be considered only for patients with a history of prior excessive alcohol consumption, persistently abnormal baseline AST values, or chronic hepatitis B or C infection. At intervals of every 4-8 weeks the AST, ALT, and albumin levels should be monitored. Routine surveillance liver biopsies are not recommended for RA patients receiving traditional doses of MTX. However, a biopsy should be performed if a patient develops persistent abnormalities on liver blood tests. These are defined as elevations (above the upper limit of laboratory normal) in the AST in 5 of 9 determinations within a given 12-month interval (6 of 12 if tests are performed monthly) or a decrease in serum albumin below the normal range. The recommendations for monitoring and selection of patients for liver biopsy identify patients at potential risk for CSLD, and thus significantly reduce the number or patients who would be exposed to this procedure. Close monitoring is essential to reduce the risk of unrecognized serious liver disease. These recommendations should be revised as necessary to reflect new and compelling information.

Arthritis, Rheumatoid↗
PubMed1994

Technetium-99m sestamibi myocardial perfusion imaging in the emergency room evaluation of chest pain.

OBJECTIVES: The purpose of this investigation was to evaluate the practicality and short-term predictive value of acute myocardial perfusion imaging with technetium-99m sestamibi in emergency room patients with typical angina and a normal or nondiagnostic electrocardiogram (ECG). BACKGROUND: Accuracy of emergency room chest pain assessment may be improved when clinical and ECG variables are used in conjunction with acute thallium-201 myocardial perfusion imaging. Technetium-99m sestamibi is a new radioisotope that is taken up by the myocardium in proportion to blood flow, but unlike thallium-201, it redistributes minimally after injection. Technetium-99m sestamibi can thus be injected during chest pain, and images acquired 1 to 2 h later (when patients have been clinically stabilized) will confirm whether abnormalities of perfusion were present at the time of injection. METHODS: One hundred two emergency room patients with typical angina (on the basis of a standardized angina questionnaire) and a normal or nondiagnostic ECG had a technetium-99m sestamibi injection during symptoms and were followed up for occurrence of adverse cardiac events (cardiac death, nonfatal myocardial infarction, coronary angioplasty, coronary surgery or coronary thrombolysis). RESULTS: Univariate predictors of cardiac events included the presence of three or more coronary risk factors (p = 0.009, risk ratio 3.3) and an abnormal or equivocal acute technetium-99m sestamibi scan (p = 0.0001, risk ratio 13.9). Multivariate regression analysis identified an abnormal perfusion image as the only independent predictor of adverse cardiac events (p = 0.009). Of 70 patients with a normal perfusion scan, only 1 had a cardiac event compared with 15 patients with equivocal scans or 17 patients with abnormal scans, with a cardiac event rate of 13% and 71%, respectively (p = 0.0004). CONCLUSIONS: Initial myocardial perfusion imaging with technetium-99m sestamibi when applied in emergency room patients with typical angina and a normal or nondiagnostic ECG appears to be highly accurate in distinguishing between low and high risk subjects.

Adult↗
PubMed1994

The prevalence of serum IgG antibodies to type II collagen in American patients with rheumatoid arthritis.

Serum IgG antibody levels to native and denatured bovine type II collagen were elevated in 31.5 and 21.5% sera respectively from 200 American patients with RA. The prevalence of serum antibodies to native type II collagen is significantly higher than previously found in large studies of the prevalence of this autoantibody in Britain and Japan when using the same methodology.

Adult↗
PubMed1994

Healing of broken human chromosomes by the addition of telomeric repeats.

We have characterized and compared a series of naturally occurring chromosomal truncations involving the terminal region of the short arm of human chromosome 16 (16p13.3). All six broken chromosomes appear to have been stabilized by the direct addition of telomeric repeats (TTAGGG)n to nontelomeric DNA. In five of the six chromosomes, sequence analysis shows that the three of four nucleotides preceding the point of telomere addition are complementary to and in phase with the putative RNA template of human telomerase. Otherwise we have found no common structural features around the breakpoint regions. These findings, together with previously reported in vitro data, suggest that chromosome-healing events in man can be mediated by telomerase and that a small region of complementarity to the RNA template of telomerase at the end of a broken chromosome may be sufficient to prime healing in vivo.

Base Sequence↗
PubMed1994

Comparison of hydroxychloroquine and placebo in the treatment of the arthropathy of mild systemic lupus erythematosus.

OBJECTIVE: To compare the relative safety and efficacy of hydroxychloroquine (HCQ) and placebo (Pl) in the treatment of the articular complaints of systemic lupus erythematosus (SLE). METHODS: Seventy-one patients with mild SLE requiring < or = 10 mg of prednisone or equivalent daily and with arthritis or arthralgias were entered into a 48-week prospective, controlled, double blind multicenter trial and randomly assigned to either HCQ or Pl. RESULTS: Both HCQ and Pl were well tolerated in the 48-week trial. There were no remissions. With the exception of the patient assessment of joint pain, all other joint measures were similar between the groups. Twenty-nine patients withdrew before the end of the trial although only 2 patients withdrew for adverse drug effects. CONCLUSION: Our study found subjective pain relief as the only statistically significant difference in joint count variables from HCQ in the treatment of the articular manifestations of SLE.

Adult↗