Knowing just how effective is treatment: implications for care of cancer patients.
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Clinical Trials as Topic↗
Biomedical subjects
C J Williams
Publications and source records attributed to C J Williams.
Multicentre cross-over study of aminoglutethimide and trilostane in advanced postmenopausal breast cancer.
Trilostane and aminoglutethimide, both given with a physiological replacement dose of hydrocortisone, were randomly allocated to 112 eligible patients with postmenopausal advanced breast cancer. Following treatment failure on either drug the patient continued with the other, if they were in a suitable clinical condition. Sixty-three patients initially received trilostane, of whom 33 subsequently received aminoglutethimide; 49 patients initially had aminoglutethimide and 14 of these then received trilostane. Both groups of patients were comparable in all respects. There was no difference in the response rate to either drug or in the average time to disease progression for the two drugs. Of the 47 patients who received both drugs, nine (19%) showed a response to both, indicating no cross-resistance. Side effects were seen to both drugs in approximately half the patients; these were mainly gastrointestinal symptoms with trilostane and rashes and drowsiness with aminoglutethimide. There was no evidence of cross-over patient susceptibility to side effects.
Administration, Oral↗
Variability in automatic activation as an unobtrusive measure of racial attitudes: a bona fide pipeline?
The research examines an unobtrusive measure of racial attitudes based on the evaluations that are automatically activated from memory on the presentation of Black versus White faces. Study 1, which concerned the technique's validity, obtained different attitude estimates for Black and White participants and also revealed that the variability among White participants was predictive of other race-related judgments and behavior. Study 2 concerned the lack of correspondence between the unobtrusive estimates and Modern Racism Scale (MRS) scores. The reactivity of the MRS was demonstrated in Study 3. Study 4 observed an interaction between the unobtrusive estimates and an individual difference in motivation to control prejudiced reactions when predicting MRS scores. The theoretical implications of the findings for consideration of automatic and controlled components of racial prejudice are discussed, as is the status of the MRS.
Black or African American↗
Three new point mutations in type II procollagen (COL2A1) and identification of a fourth family with the COL2A1 Arg519-->Cys base substitution using conformation sensitive gel electrophoresis.
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Achondroplasia↗
Evidence against either a premature stop codon or the absence of obese gene mRNA in human obesity.
Obese (ob) gene expression in abdominal subcutaneous adipocytes from lean and obese humans was examined. The full coding region of the ob gene was isolated from a human adipocyte cDNA library. Translation of the insert confirmed the reported amino acid sequence. There was no difference in the sequence of an reverse transcription PCR product of the coding region from five lean and five obese subjects. The nonsense mutation in the ob mouse which results in the conversion of arginine 105 to a stop codon was not present in human obesity. In all 10 human cDNAs, arginine 105 was encoded by CGG, consequently two nucleotide substitutions would be required to result in a stop codon. To compare the amount of ob gene expression in lean and obese individuals, radiolabed primer was used in the PCR reaction with beta-actin as a control. There was 72% more ob gene expression (P < 0.01) in eight obese subjects (body mass index, BMI = 42.8 +/- 2.7) compared to eight lean controls (BMI = 22.4 +/- 0.8). Regression analysis indicated a positive correlation between BMI and the amount of ob message (P < 0.005). There was no difference in the amount of beta-actin expression in the two groups. These results provide evidence that ob gene expression is increased in human obesity; furthermore, the mutations present in the mouse ob gene were not detected in the human mRNA population.
Adult↗
Heritable diseases of cartilage caused by mutations in collagen genes.
Osteoarthritis (OA) is a heterogeneous disease resulting from multiple pathogenic mechanisms. Several forms of OA are inherited in an autosomal Mendelian pattern. Recent studies have identified a variety of mutations in the type II collagen gene, which encodes the main collagenous component of articular cartilage in some forms of familial OA and other heritable diseases of cartilage, including Stickler syndrome and the chondrodysplasias. Mutations in the type X collagen gene, which encodes a major collagen of growth plate cartilage, have been identified in the Schmid type of osteochondrodysplasias. Identification of additional mutations in cartilage collagen genes in familial OA will broaden our understanding of the pathogenesis of the disease, and may permit the preventive treatment of individuals at risk.
Amino Acid Sequence↗
Pharmacoeconomics of intravenous antibiotic use in serious infection.
A pharmacoeconomic study of 15 antibiotics available in Barbados was performed. The antibiotics studied were amoxycillin/clavulanate, ampicillin, ampicillin/sulbactam, cefazolin, cefotaxime, ceftazidime, ceftriaxone, clindamycin, cloxacillin, cotrimoxazole, gentamicin, imipenem, metronidazole, piperacillin, piperacillin/tazobactam, and vancomycin. The costs of use of these compounds were calculated for a five-day course using a formula comprising eight categories: antibiotic purchase cost, maintenance of intravenous access, drug delivery cost, drug monitoring cost, dose readjustment, general monitoring cost, 'sharps' disposal cost and adverse effects. The costs of adverse effects were not included in this study due to lack of accurate data. The total cost of antibiotic use (in U.S. dollars) ranged from $42.52 to $463.73 per five-day course. Generic compounds were less expensive ($45.52 - $98.23) than brand-name compounds ($106.18 - $106.18 - $463.73). Antibiotic purchase costs accounted for proportions of total costs ranging from 7 to 93%. Non-drug costs represented a much greater proportion of total costs of generic compounds. For most compounds the non-drug costs were related to the frequency of dosing, but for gentamicin the non-drug costs were relatively higher because of the need for monitoring of serum gentamicin levels. Efficacy and freedom from side-effects will remain the most important determinants in the choice of antibiotic therapy. However, pharmacoeconomic analyses can provide prescribers with the information required to make cost-effective choices for treatment of their patients.
Anti-Bacterial Agents↗
Enkephalinergic rostral hypothalamic neurones do not project to the intermediate PAG in the rat.
Retrograde transport of fluorescent latex microspheres was combined with immunocytochemistry to determine whether enkephalinergic neurones in the rostral hypothalamus project to the intermediate periaqueductal grey. Distributions of retrogradely labelled neurones and neurones immunoreactive for enkephalins were as expected from previous studies. However, very few neurones contained both markers suggesting that enkephalinergic neurones in the rostral hypothalamus do not project to the periaqueductal grey at this level. A series of control experiments was carried out on a pathway with a known enkephalinergic component to confirm the compatibility of this combination of techniques.
Animals↗
Rescue of T cell-specific V(D)J recombination in SCID mice by DNA-damaging agents.
Assembly of antigen receptor V (variable), D (diversity), and J (joining) gene segments requires lymphocyte-specific genes and ubiquitous DNA repair activities. Severe combined immunodeficient (SCID) mice are defective in general double-strand (ds) DNA break repair and V(D)J coding joint formation, resulting in arrested lymphocyte development. A single treatment of newborn SCID mice with DNA-damaging agents restored functional, diverse, T cell receptor beta chain coding joints, as well as development and expansion of thymocytes expressing both CD4 and CD8 coreceptors, but did not promote B cell development. Thymic lymphoma developed in all mice treated with DNA-damaging agents, suggesting an interrelation between V(D)J recombination, dsDNA break repair, and lymphomagenesis.
Animals↗
Familial spondyloepiphyseal dysplasia tarda, brachydactyly, and precocious osteoarthritis associated with an arginine 75-->cysteine mutation in the procollagen type II gene in a kindred of Chiloe Islanders. I. Clinical, radiographic, and pathologic findings.
OBJECTIVE: To characterize a kindred of Chiloe Islanders with spondyloepiphyseal dysplasia tarda (SEDT), brachydactyly, precocious osteoarthritis (OA), and intraarticular calcification. METHODS: Sixteen family members underwent a complete physical examination, anthropometric measurements, radiographic studies of the spine and peripheral joints, and analysis of the type II procollagen gene (COL2A1). RESULTS: Seven family members presented with SEDT, brachydactyly, precocious OA, and periarticular calcification while 2 others had the same syndrome but without brachydactyly. The inheritance was autosomal dominant, and the disease cosegregated with a base substitution in the COL2A1 gene. CONCLUSION: The syndrome o SEDT, precocious OA, and brachydactyly in a kindred of Chiloe Islanders is associated with a point mutation in 1 allele of the COL2A1 gene. The relationship of this type of SEDT to familial calcium pyrophosphate dihydrate deposition disease and idiopathic hip dysplasia, both endemic in Chiloe Islanders, needs to be further investigated.
Adult↗
A single base mutation in the type II procollagen gene (COL2A1) that converts glycine alpha 1-247 to serine in a family with late-onset spondyloepiphyseal dysplasia.
A search for mutations in the gene for type II procollagen (COL2A1) was carried out in a family with late-onset spondyloepiphyseal dysplasia resulting in short sature, restricted mobility and severe pain in joints, deforming arthritis in the hips, and claudication. Analysis of the HindIII and VNTR polymorphisms at the COL2A1 gene in the family raised the possibility that the gene cosegregated with the disease. Screening for mutations in the COL2A1 gene using PCR-denaturing gradient get electrophoresis suggested a sequence variation in exon 19 of one allele of the COL2A1 gene in the proband. Direct sequencing of the PCR products for exon 19 revealed a single base mutation that converted the codon of -GGT- for glycine at alpha 1-247 to -AGT-, a codon for serine. The mutant that converted the present in all affected family members, but absent in nonaffected members and in a group of 50 unrelated healthy individuals. It was also absent in 20 unrelated patients with chondrodysplasia and 30 unrelated patients with early-onset osteoarthritis.
Adult↗
Homosexual foot fetishism.
262 respondents from an organization for homosexual foot fetishists provide information from a broader sample than clinical cases and allow examination of the effects of sexual preference on fetishism. Data show a wide range of feet/footwear objects to be arousing. Such interests were often associated with particular types of men, yet interests were subject to change over time. Fetishistic arousal rested on both sensual and symbolic aspects of the fetish. Symbolically, it was the theme of "masculinity" that made male feet/footwear arousing, showing parallels to "femininity" evoked by female feet/footwear for male heterosexual fetishists. For many of the respondents, fetishism did not seem to be a substitute for living persons. Respondents had intimate relationships and were able to incorporate their fetish interests into stable relationships and less intimate ones. Considerable involvement in sadomasochistic practices was also found as was involvement in the gay world. Finally, nothing about a fetishistic interest seemed to preclude the development of subcultural forms around the practice.
Adult↗
Informed consent in European multicentre randomised clinical trials--are patients really informed?
This study was designed to examine the standard of consent used by investigators in European randomised clinical trials (RCT). The participants of 12 multicentre RCTs published in the European Journal of Cancer in the years 1990-1992 were asked to complete a short questionnaire regarding their practice of obtaining consent in the trial reported. Anonymity was assured. Replies were received from 60 of 88 clinicians contacted. Data showed that 12% of clinicians did not inform their patients about the trial prior to randomisation. Thirty-eight per cent of clinicians did not always tell patients that they had been assigned to their treatment randomly. Only 32% of clinicians used written consent, 21% used written information without obligatory signing, 42% used verbal consent, and in 5% no consent was sought. Even when information was given, only 58% of clinicians gave full information on all aspects of the trial and 42% gave information on the proposed treatment arm only (27% revealing inclusion in an RCT). When examined by geographical origin, clinicians in northern Europe were more likely to obtain full consent than those from southern Europe. Similarly, the level of consent was higher in trials of supportive care than in trials testing curative or palliative antitumour therapies.
Communication↗
Sleep deprivation as a diagnostic instrument.
A 59-year-old man with chronic treatment-resistant depression developed severe cognitive impairment. The severity of depression and the mode of presentation led to difficulty in diagnosis between a dementing disorder and a depressive illness. The diagnostic conundrum was resolved by the use of sleep deprivation (SD), which demonstrated clear subjective and objective improvements in his condition. These changes were quantified by a range of psychometric tests, which showed that initial deficits in cognitive performance improved temporarily after SD, and these improvements were maintained after effective treatment of the depression with electroconvulsive therapy.
Cognition Disorders↗
Monitoring and preventive care of the paralyzed patient in respiratory failure.
It is our belief, based on our experience with the Dulin-Williams protocol, that the safe use of a continuous-infusion NMBA is optimized when a constant current peripheral nerve stimulator is used to monitor the depth of neuromuscular blockade. This protocol should facilitate the chance of adverse effects, thereby increasing the quality of patient care and outcomes within the critical care setting.
Anxiety↗
Lipid data from NHLBI veteran twins: interpreting genetic analyses when model assumptions fail.
Analyses were performed on lipid data from the NHLBI Veteran Twin Study. The analyses focused on longitudinal multivariate models, describing how the genetic effects on lipids vary over time. Our pedigree-based model selection approach allows simultaneous estimation of both covariance structure parameters and regression parameters. The analyses reveal strong correlations between additive genetic effects over time, implying that genetic effects on lipids are somewhat constant throughout the life span represented within this sample. Both univariate preliminary analyses and robust fitting applied to the longitudinal models indicate that several assumptions underlying the twin analyses are violated. Although variance component and correlation parameter estimates are not much changed by robust fitting analyses, questions remain about the behavior of parameter estimates in multivariate genetic models under departures from model assumptions.
Humans↗
Spondyloepiphyseal dysplasia and precocious osteoarthritis in a family with an Arg75-->Cys mutation in the procollagen type II gene (COL2A1).
Direct sequencing of polymerase chain reaction (PCR)-amplified genomic DNA from a patient with spondyloepiphyseal dysplasia and precocious osteoarthritis revealed a single-base change in exon 11 of the type II procollagen gene (COL2A1), which produces an Arg-->Cys mutation in one allele. The proband is a member of a large Chilean kindred presenting with chondrodysplasia of the hips, knees, shoulders, elbows, and spine associated with severe, early-onset osteoarthritis. All affected individuals exhibit mildly short stature; in addition, five out of seven affected family members display shortened metacarpals or metatarsals. DNA from affected and unaffected family members was PCR-amplified and analysis of restriction digests of the products determined that the mutation segregated with the disease with a lod score of 2.2 at zero recombination. The mutation, which resides in the triple-helical region of type II procollagen at amino acid position 75, is the second example of an Arg-->Cys mutation in the COL2A1 gene in heritable cartilaginous disease and is the first example of a point mutation in the amino terminal region of the alpha 1(II) chain, that results in a spondyloepiphyseal dysplastic phenotype.
Adolescent↗
Multicentre cross over study of aminoglutethimide and trilostane in advanced postmenopausal breast cancer.
Trilostane and Aminoglutethimide, each given with a physiological replacement dose of hydrocortisone, were randomly allocated to 72 eligible postmenopausal advanced breast cancer patients; following treatment failure on either drug the patient continued with the other drug, if in a suitable clinical condition. Thirty-eight patients initially received Trilostane of whom 19 subsequently received Aminoglutethimide; 34 patients initially had Aminoglutethimide and seven of these then received Trilostane. Both groups of patients were comparable in all respects. There was no difference in the objective response rate to either drug, Trilostane 11/38 = 29%, Aminoglutethimide 12/34 = 35%, nor in the average time to disease progression for the two drugs, Trilostane 64 weeks, Aminoglutethimide 68 weeks. Of the 26 patients who received both drugs, four showed a response to both suggesting no cross resistance. Side effects were seen to both drugs in approximately half of the patients, but were mainly gastro-intestinal with Trilostane and rash and drowsiness with Aminoglutethimide. There was no evidence of cross over patient susceptibility to side effects.
3-Hydroxysteroid Dehydrogenases↗