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Biomedical subjects

C L Hill

Publications and source records attributed to C L Hill.

At least 37 records · Page 2Linked to original sources

Health related quality of life in a population sample with arthritis.

OBJECTIVE: To determine the prevalence and health related quality of life of a community sample of people with arthritis and compare it with persons with other chronic diseases and the healthy population in South Australia. METHODS: A representative population survey by trained interviewers in autumn 1995 using a multi-stage, systematic, clustered area sample of 4200 urban and country households. There were 3001 (73.6%) respondents aged 15 or over. Subjects were asked, "Have you ever been told by a doctor that you have arthritis?" and "What type?", in addition to the Medical Outcome Survey Short Form-36 (SF-36) health status survey. RESULTS: Medically confirmed arthritis was self-reported in 666 (22.1%) as osteoarthritis (OA) (8.6%), rheumatoid arthritis (RA) (4.0%), and other, or unspecified arthritis (9.6%). People with arthritis were more likely to be female, aged, and of lower socioeonomic status. SF-36 scores were compared to nonarthritic subjects and adjusted for differences in age, sex, and occupational status. Scores were significantly lower for respondents with arthritis, compared with the rest of the population across all subscales of the SF-36 (p<0.05). This was most marked in the subscales measuring physical function and pain. CONCLUSION: Self-reported arthritis is common in the South Australian population, particularly in those aged over 65 years. Arthritis has a major impact on the health related quality of life in the community setting.

Adolescent↗

Potent inhibition of respiratory syncytial virus by polyoxometalates of several structural classes.

A series of polyoxometalates (POM) were synthesized and evaluated for anti-respiratory syncytial virus (RSV) activity. POM containing zirconium, tungsten, silicon, platinum, niobium or germanium of a variety of structural types have been evaluated. Sixteen of the compounds had very striking anti-RSV activity against a clinical isolate, Utah 89, with median effective concentration (EC50) values < or = 3 microM and selective indices > 80 as determined by viral cytopathic inhibition effect, neutral red uptake and virus yield reduction assays. The EC50 values for all three assays correlated very well (Pearson correlation coefficients > 0.90). POM containing sodium cations were totally inactive. Germanium-, niobium-, tin- and zirconium-containing compounds were found to be highly potent and selective. The antiviral activity was not cell line-dependent. The median cytotoxic concentration (IC50) values were generally greater than 100 microM. The compounds were also comparably active against a known laboratory RSV strain, A2, as well as other RSV strains. To detect any virus strain-specific inhibitory activity, seven POM were tested against other RSV strains; all were nearly equally inhibitory to the human virus strains, suggesting no strain specificity. Timing studies suggested that these compounds were most inhibitory during virus adsorption and penetration, although RSV was still significantly inhibited when the compound was added 3 h post-infection; which is considered well into the eclipse period. These data suggest that these potent, non-toxic compounds should be further studied as potential chemotherapeutic agents for treating RSV infections.

Animals↗

Diet and arthritis.

Choice of diet is one way in which an individual can influence his/her own health, and it is to be expected that patients will seek their physician's expert opinion regarding dietary matters. Respect for the legitimacy of these enquiries and balanced informed discussion, which includes general advice for a prudent diet, as well as disease-specific recommendations when indicated, can be the key to a productive relationship between patients and physician. The issue of dietary advice has an impact on the management of most forms of arthritis including osteoarthritis (obesity/energy balance), gout (dietary purines, energy balance, alcohol, fluid intake) and rheumatoid arthritis (n-3 fatty acids). Food hypersensitivity appears to be a rare cause of polyarthritis, and elimination diets and fasting have little or no place in routine practice. Strategies under investigation include oral tolerization, the utility of which remains to be established.

Arthritis↗

Managing vocabulary for a centralized clinical system.

The clinical computing environment at Columbia-Presbyterian Medical Center is organized around a centralized database of coded patient information collected from various ancillary sources. The Medical Entities Dictionary (MED) is the central repository for the controlled vocabulary used to encode the patient data. The MED is composed of terms used in the ancillary departments and, as such, changes in the source vocabularies must be maintained in the MED. The MED also contains some basic knowledge about the terms, and sophisticated maintenance tools have been developed that take advantage of this knowledge. This paper describes the success of the knowledge-based approach by describing the techniques used in two tasks: addition of a new vocabulary and maintenance of an existing one.

Clinical Laboratory Information Systems↗

Synthesis, characterization, and biological activity of a new potent class of anti-HIV agents, the peroxoniobium-substituted heteropolytungstates.

The mono- and trisubstituted peroxyniobium polyoxotungstates of formulas [(CH3)3NH]7[Si-(NbO2)3W9O37], Cs7[Si(NbO2)3W9O37], alpha-K5[Si(NbO2)W11O39] and alpha-[(CH3)3NH]5[Si(NbO2)-W11O39], have been prepared, purified, and characterized spectroscopically by 29Si NMR, 183W NMR, and IR. The presence of peroxo groups was verified by the yellow color of the product and quantified by iodometric titration. The potency of both the complexes and the precursor complexes was evaluated in human peripheral blood mononuclear cells (PBMC) acutely infected with human immunodeficiency virus type 1 (HIV-1). Hexaniobate (K7H[Nb6O19]) was the least effective with a median effective concentration (EC50) of > 100 microM, while Cs7[Si(NbO2)3W9O37] was one of the most effective compounds with an EC50 of 1.0 microM. None of the compounds were toxic to uninfected PBMC with the exception of alpha-K8[SiW11O39], which had a median inhibitory concentration (IC50) of 79 microM. The potency and selectivity of the complexes against HIV-1 reverse transcriptase was also evaluated and shown to be quite high (IC50 values from 0.03 to 0.06 microM). The trimethylammonium salts of the complexes were tested for their ability to inhibit the interaction between gp120 and CD4 using a cell-free system. The complex [(CH3)3NH]7[Si(NbO2)3W9O37] inhibited this interaction by 70% at 25 microM.

Antiviral Agents↗

Reduced E-cadherin expression correlates with increased invasiveness in colorectal carcinoma cell lines.

A reduction in cell adhesiveness and cell invasion are essential steps in tumour progression to metastasis. In the present study two out of seven colorectal carcinoma cell lines exhibited reduced expression of the cell-cell adhesion molecule E-cadherin as assessed by immunofluorescence. The same two cell lines were invasive in the collagen gel and membrane invasion culture system invasion assays. Addition of anti-E-cadherin antibody to a non-invasive carcinoma cell line caused the cells to assume a dissociated morphology on plastic and to become invasive in collagen gels. This demonstrates a causal role for E-cadherin in the maintenance of intercellular adhesion and the suppression of tumour cell invasion and possibly metastasis in colorectal tumour cells.

Adenocarcinoma↗

Abnormal bone mineral metabolism after long-term anticonvulsant treatment.

OBJECTIVE: To present a case of anticonvulsant-induced disturbances of bone mineral metabolism associated with long-term phenytoin treatment. CASE SUMMARY: An 87-year-old woman was hospitalized with generalized acroparesthesia. Her medical history was significant for grand mal epilepsy, which had been treated with phenytoin for more than ten years. On admission she was found to be hypocalcemic, and her alkaline phosphatase concentration was markedly elevated. DISCUSSION: Further investigations revealed that the patient's serum concentration of 25-hydroxycalciferol was well below the expected range. Phenytoin treatment was withdrawn, and calcitriol supplementation commenced. Ten weeks later she was normocalcemic, and the calcitriol dosage was reduced. Radiologic investigations at this time revealed an ununited hip fracture, as well as widespread evidence of bone demineralization. CONCLUSIONS: Minor elevations of liver enzymes observed in association with anticonvulsant treatment may reflect hepatic microsomal enzyme induction. Marked elevation of serum alkaline phosphatase, particularly when seen in concert with hypocalcemia, may be markers of anticonvulsant-induced bone disease. Under these circumstances, further radiologic investigations and measurement of the vitamin D serum concentration should be undertaken.

Aged↗

The role of the cell-cell adhesion molecule E-cadherin in large bowel tumour cell invasion and metastasis.

It has been suggested that the selective loss of E-cadherin expression can generate invasiveness in human carcinoma cells and might be a predictor of metastasis. Frozen sections of samples from 44 patients, 43 with suspected large bowel cancer and one with a liver recurrence were examined for E-cadherin expression using the antibody 6F9 specific for the human E-cadherin molecule. Twelve of the 40 patients with carcinoma already had lymph node involvement at the time of surgery. Samples from the primary carcinomas of only nine of these 12 patients showed reduced E-cadherin expression. However, the one lymph node with metastatic spread examined did show reduced E-cadherin expression. Four of the 40 carcinoma patients had liver involvement at the time of surgery. The primary carcinoma samples from only three of these four patients showed reduced E-cadherin expression. In addition only two out of the three liver metastases examined showed reduced expression. The primary carcinoma samples from seven patients with no evidence of tumour spread also exhibited reduced expression. Overall, analysis of the data suggests that there is no absolute correlation between reduced E-cadherin expression and tumour spread in carcinomas of the large bowel.

Adenocarcinoma↗

Synthesis and virucidal activity of a water-soluble, configurationally stable, derivatized C60 fullerene.

The bis(monosuccinimide) derivative of p,p'-bis(2-aminoethyl)diphenyl-C60 (compound 1), prepared by the fulleroid route, is active against human immunodeficiency virus type 1 (HIV-1) and HIV-2 (50% effective concentration [EC50] averaging approximately 6 microM) in acutely or chronically infected human lymphocytes and is active in vitro against 3'-azido-3'-deoxythymidine-resistant HIV-1 (EC50, approximately 3 microM). The virucidal properties of compound 1 were confirmed by virus inactivation assays. Compound 1 was noncytotoxic up to 100 microM in peripheral blood mononuclear cells and H9, Vero, and CEM cells. In cell-free assays, whereas the fullerene showed comparable activity against HIV-1 reverse transcriptase and DNA polymerase alpha (50% inhibitory concentration of approximately 5 microM), it demonstrated selective activity against HIV-1 protease.

Acquired Immunodeficiency Syndrome↗

Physician use of computers: is age or value the predominant factor?

One common explanation for the failure to achieve broad physician utilization of computer applications has been the suggestion that "We can't teach older individuals to use computers." To investigate this hypothesis, we examined utilization patterns for the Clinical Information System (CIS) at Columbia Presbyterian Medical Center (CPMC). We analyzed CIS usage for 925 attending physicians who were listed as an admitting or attending physician or surgeon for at least one patient during the year 1992. Sixty-one percent (561/925) of the attending physicians used the system at least once during the year. Sixty five percent (186/287) of the physicians who admitted at least 50 cases used the system at least 120 times during the year. The most surprising aspect of our analysis was that physicians in their late 60's and early seventies actually used the system more than their peers who were in their late 50's. Patterns of use by age group were similar for those who admitted many and few patients to the hospital. Using linear regression and chi squared analysis, we found that age is correlated (p < 0.002) with levels of physician use (inquiries per case), although age can explain (r-squared) only 3% of the observed variation in utilization patterns. We also found that there was significant variation in utilization (inquiries per case) by attendings in different departments (p < 0.007). However, the variation within departments was also large. We conclude that age and type of practice are statistically significant but not major factors in predicting which attendings will use the system. Growth rates over time (19% year to year increase in the average number of different users per day) indicate that, if present trends continue, virtually all physicians regardless of age will use the Clinical Information System for results review. We continue to feel that providing value, access and ease of use are the most important determinants for success.

Adult↗

Synthesis, characterization, and anti-human immunodeficiency virus activity of water-soluble salts of polyoxotungstate anions with covalently attached organic groups.

The cesium and tetramethylammonium (TMA) salts of polyoxotungstate anions with covalently attached organosilyl groups of formula [(RSi)2O]SiW11O39(4-), where R = CH2CH2COCH3, (CH2)3CN, and CH==CH2 (1-R, cesium salt, unless otherwise noted) have been prepared, purified, and spectroscopically characterized. The water solubility (25 degrees C) of these 10 new compounds ranges from 0.14 mM to 2.16 mM. All appear to be stable in aqueous media over a period of several hours as assessed by 1H NMR. The activities (EC50) of the new compounds against human immunodeficiency virus in primary human lymphocytes range from 3.3 microM to 39.0 microM. Their toxicities (IC50) are all greater than 100 microM. The inhibition constants of the new compounds against purified virion-derived HIV-1 reverse transcriptase are in the 1-10 microM range.

Anions↗

Induction of resistance to 6-thioguanine and cytarabine by a range of anticancer drugs in Chinese hamster AA8 cells.

A mutagenicity assay using AA8 Chinese hamster cells has been used to explore the potential of some currently used clinical anticancer drugs to induce cells resistant to 6-thioguanine and cytarabine. Preliminary experiments gave evidence of a "low dose" and "high dose" resistance to cytarabine, and subsequent work considered only the latter of these events. When ethyl methane sulphonate was used as a reference mutagen, induced resistance to cytarabine developed substantially later and at a lower frequency than resistance to 6-thioguanine. Of the clinical drugs tested, carmustine showed the highest ability to induce either 6-thioguanine or cytarabine resistant cells. Bleomycin, daunomycin and amsacrine showed moderate ability, while vincristine was essentially inactive in these assays. Such information could potentially be used in selecting new drug combinations or timing of drug administration in cancer chemotherapy.

Amsacrine↗

Anti-HIV-1 activity, toxicity, and stability studies of representative structural families of polyoxometalates.

The anti-HIV-1 activity and toxicity of representative structural families of polyoxotungstates in human lymphocytes was determined. The 21 compounds examined include those derived from the following structural families: [NaSb9W21O86]18- (HPA-23), Xn+W12O40(8-n)- (Keggin), P2W18O62(6-) (Wells-Dawson), W6O19(2-) (Lindqvist), [NaP5W30O110]14- (Preyssler), and W10O32(4-) (decatungstate). The molecular architecture of each of these structural families is constituted principally by a network of bonds between d0 WVI and oxide ions. Of these, 10 show median effective concentration (EC50) values of approximately 1 microM and six have marked toxicity with a median inhibitory concentration (IC50) of less than 50 microM. Only compounds containing more than six metal atoms showed appreciable antiviral activity. Beyond this, however, no marked correlation existed between the molecular size, charge, or charge density of the polyoxometalates and their anti-HIV-1 activity. Examination of an exemplary class of polyoxotungstates, the phosphotungstates of formula A- and B-PW9O34(9-) under physiological conditions (buffered neutral aqueous media), illustrates that both isomers equilibrate rapidly to generate the same distribution of products and that this distribution depends principally on the buffer. These heretofore unappreciated complexities in the chemistry of these compounds under neutral aqueous conditions indicates interpretation or evaluation of these compounds in cell culture and other biological screens must be done with care.

Antimony↗

The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability.

The Yale-Brown Obsessive Compulsive Scale was designed to remedy the problems of existing rating scales by providing a specific measure of the severity of symptoms of obsessive-compulsive disorder that is not influenced by the type of obsessions or compulsions present. The scale is a clinician-rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms) (total range, 0 to 40), with separate subtotals for severity of obsessions and compulsions. In a study involving four raters and 40 patients with obsessive-compulsive disorder at various stages of treatment, interrater reliability for the total Yale-Brown Scale score and each of the 10 individual items was excellent, with a high degree of internal consistency among all item scores demonstrated with Cronbach's alpha coefficient. Based on pretreatment assessment of 42 patients with obsessive-compulsive disorder, each item was frequently endorsed and measured across a range of severity. These findings suggest that the Yale-Brown Scale is a reliable instrument for measuring the severity of illness in patients with obsessive-compulsive disorder with a range of severity and types of obsessive-compulsive symptoms.

Adult↗

The nonluteal porcine ovary as a source of angiogenic activity.

Nonluteal ovarian tissue extracts were tested for their ability to stimulate migration and proliferation of cultured bovine capillary endothelial cells. Stimulation of migratory and proliferative activity was found in the 105,000 X g supernatant of homogenates of either whole nonluteal porcine ovaries or isolated theca (follicular walls). Maximal proliferative and migratory activity was obtained with 1-10 micrograms homogenate protein. Neither follicular fluid nor extracts of granulosa cells showed significant activity when tested over a broad concentration range. The proliferative and migratory activities were associated with a heat-labile, nondialyzable, protease-sensitive fraction that was soluble in 40%, but not 60% (NH4)2SO4. The tissue extracts that effectively stimulated growth and migration of capillary endothelial cells in vitro also stimulated the formation of new capillary blood vessels in an angiogenesis assay performed on chick chorioallantoic membranes.

Allantois↗

Retromastoid microsurgical approach to vascular compression of the eighth cranial nerve.

In our series of 10 patients, the age ranged between 31 and 69 years. Seven patients were followed for from 1-2 1/2 years. Complaints consisted of tinnitus, vertigo, or both. Vegatative symptoms consisting of nausea or vomiting were minimal or absent. Audiometry revealed a varying neurosensory loss. Vestibular hypoexcitability was a common finding. Good discrimination appeared to indicate a vascular loop rather than hydrops. The neuroradiological work-up was unremarkable. Treatment consisted of neurovascular decompression of the VIIth nerve by microdissection. The approach used was a retromastoid incision with a bony removal limited to 20 mm. Cerebrospinal fluid withdrawal and lateral decubitus positioning permitted visualization of the VIIIth nerve without retraction of the cerebellum. Lack of bleeding, rapidity of procedure and benign postoperative course are emphasized. The results on tinnitus and vertigo were satisfactory. No additional deficit was created by surgery. If the symptoms are significantly disabling, microsurgical exploration is indicated.

Adult↗