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Biomedical subjects

K James

Publications and source records attributed to K James.

At least 37 records · Page 2Linked to original sources
PubMed2000

First report of the investigation into the importance of pK(a) in the inhibition of estrone sulfatase by sulfamate containing compounds.

In an effort to rationalise the inhibitory activity of a range of aminosulfamate compounds and to further investigate the recently reported definitive pharmacophore estrone sulfatase (ES), we undertook extensive synthesis, biochemical evaluation and physicochemical property determination of a range of similar compounds. Here, we report the initial results of our study into a series of simple (aminosulfonate based) substituted phenol derivatives. Using these compounds, we investigated the role of pK(a) in the inhibition of ES. The results of the study suggest that there is a strong correlation between the inhibitory activity and the stability of the resulting O(-) anion (i.e., the pK(a) of the starting phenol).

Anions↗
PubMed2000

Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results.

BACKGROUND: A randomized trial conducted by the Gynecologic Oncology Group (GOG, study #111) in the United States showed a better outcome for patients with advanced ovarian cancer on the paclitaxel-cisplatin regimen than for those on a standard cyclophosphamide-cisplatin regimen. Before considering the paclitaxel-cisplatin regimen as the new "standard," a group of European and Canadian investigators planned a confirmatory phase III trial. METHODS: This intergroup trial recruited 680 patients with broader selection criteria than the GOG #111 study and administered paclitaxel as a 3-hour instead of a 24-hour infusion; progression-free survival was the primary end point. Patient survival was analyzed by use of the Kaplan-Meier technique. Treatment effects on patient survival were estimated by Cox proportional hazards regression models. All statistical tests were two-sided. RESULTS: The overall clinical response rate was 59% in the paclitaxel group and 45% in the cyclophosphamide group; the complete clinical remission rates were 41% and 27%, respectively; both differences were statistically significant (P =.01 for both). At a median follow-up of 38.5 months and despite a high rate of crossover (48%) from the cyclophosphamide arm to the paclitaxel arm at first detection of progression of disease, a longer progression-free survival (log-rank P =.0005; median of 15.5 months versus 11.5 months) and a longer overall survival (log-rank P =. 0016; median of 35.6 months versus 25.8 months) were seen in the paclitaxel regimen compared with the cyclophosphamide regimen. CONCLUSIONS: There is strong and confirmatory evidence from two large randomized phase III trials to support paclitaxel-cisplatin as the new standard regimen for treatment of patients with advanced ovarian cancer.

Adult↗
PubMed2000

Fine mapping of the neurally expressed gene SOX14 to human 3q23, relative to three congenital diseases.

Members of the Sox gene family encode transcription factors that have diverse and important functions during development. We have recently described the cloning of chick and mouse Sox14 and the expression of these genes in a population of ventral interneurons in the embryonic spinal cord. We report here the cloning and sequencing of the human orthologue of Sox14. Human SOX14 shows remarkable sequence conservation compared with orthologues from other vertebrate species and probably mirrors the expression of these genes in the developing brain and spinal cord. Using radiation hybrid mapping and fluorescence in situ hybridisation, we have localised SOX14 close to the sequence tagged site D3S1576 on human chromosome 3q23. Three congenital disorders have been localised to this region: blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), Charcot-Marie-Tooth neuropathy type IIB (CMT2B) and Mobius syndrome type 2 (MBS2). We have found that SOX14 is unlikely to be involved in any of these disorders because of the position of SOX14 proximal to a BPES breakpoint and the lack of SOX14 coding region alterations in BPES, CMT2B and MBS2 patients.

Amino Acid Sequence↗
PubMed2000

Multiple organ damage caused by a new toxin azaspiracid, isolated from mussels produced in Ireland.

A new type of food poisoning resulting from ingestion of mussels produced in Ireland occurred in the Netherlands in 1995 and then reoccurred in Ireland in 1997. As the causative agent, azaspiracid, was isolated in pure form and revealed to have a structure entirely unlike other known algal toxins, in vivo studies with mice were carried out to elucidate the pathological injuries caused by the toxin. By per os administration, the toxin caused necrosis in the lamina propria of the small intestine and in lymphoid tissues such as thymus, spleen and the Peyer's patches. Both T and B lymphocytes were injured. Additionally a fatty change was observed in the liver. These injuries distinctly differed from those caused by the representative diarrhetic shellfish toxin, okadaic acid.

Administration, Oral↗
PubMed2000

Role for CD40-CD40 ligand interactions in the immune response to solid tumours.

CD40-mediated interactions play an important role in the response to infections, transplantation, and cancer by affecting the development, activation, proliferation and differentiation of a variety of immune cells. In the current study we examined the role of CD40-mediated interactions in immune responses to bladder, pancreatic and breast carcinomas as well as melanoma cell lines using soluble human CD40L (rhCD40L) or anti-CD40 mAb in vitro. CD40 expression was readily detected in a large proportion of the cell lines and was augmented but not induced de novo by treatment with IFNgamma. Treatment of CD40-positive cell lines with rhCD40L or anti-CD40mAb enhanced cell surface expression of ICAM-1 and FAS and stimulated the production of IL-6, IL-8, GROalpha, GM-CSF and TNFalpha but not IL-4, IL-10, TGFbeta, MCP-1, RANTES, MIP-1beta, or IP-10. In addition, incubation of CD40+ tumour cell lines with immobilised rhCD40L or anti-CD40 mAb in vitro resulted in significant inhibition of proliferation and a corresponding decrease in viability. This CD40-mediated inhibition of cell growth was due, at least in part, to alterations in cell cycle and the induction of apoptosis. Transfection of CD40-negative tumour cell lines with the cDNA for CD40 conferred responsiveness to rhCD40L and anti-CD40 antibody. Finally, the presence of CD40 on the surface of carcinoma lines was found to be an important factor in the generation of tumour-specific T cell responses.

3T3 Cells↗
PubMed2000

Mechanisms of action of intravesical bacille Calmette-Guérin: local immune mechanisms.

The local immune response to mycobacteria is complex, but mycobacterial antigen presentation by phagocytes to T helper cells is the pivotal interaction. Bacille Calmette-Guérin (BCG) vaccination is associated with the development of antituberculosis immunity but not necessarily with antitumor immunity. Animal studies have shown that an intact host immune system is required for the antitumor activity of BCG. Immunosuppressed and, particularly, T cell-depleted individuals fail to respond to BCG immunotherapy. Clinical and laboratory evidence suggest that the antitumor activity is concentrated at the site of BCG administration, which reinforces the view that local immune mechanisms are responsible for this phenomenon.

Administration, Intravesical↗
PubMed2000

Managed care regulations: impact on quality?

Over the last decade, the general public and providers have become increasingly concerned about the quality of care provided by managed care organizations. This article focuses on state and federal legislative proposals to protect quality, and the potential tradeoffs involved with increased regulatory oversight of managed care proposals. In enacting managed care legislation, policy makers should balance the costs potential with the extent to which proposed policies will protect consumers from harm, enhance the operation of the market, or affect quality of care, access to services or choice of providers.

Continuity of Patient Care↗
PubMed2000

Development of the antinuclear and anticytoplasmic antibody consensus panel by the Association of Medical Laboratory Immunologists.

The Association of Medical Laboratory Immunologists (AMLI) have developed a panel of antinuclear and anticytoplasmic antibody consensus sera that can be useful for enzyme immunoassay (EIA), Ouchterlony, and immunofluorescence assay methods. It was developed to assist in the evaluation of newly available EIA methods for the detection of autoantibodies. The panel of sera was evaluated in several clinical laboratories and a large number of laboratories owned by manufacturers of clinical autoantibody testing kits. The majority of sera performed well for the EIAs in both the clinical laboratories and the manufacturers' laboratories, but some samples had discrepant results. A major source of discrepancy is the current inability of the EIA results to be directly compared in a quantitative way as no standardization exists. The evaluation demonstrated lower sensitivity of detection by the Ouchterlony method. The limited evaluation of the sera with immunoblotting and Western blotting did not show good agreement with other methods. Further work must be done to standardize blotting methods prior to their use in routine clinical testing. The sera are now available to vendors and clinical laboratories for use in the detection of SS-A, SS-B, Sm, U1-RNP, Scl-70, Jo-1, double-stranded DNA, and centromere antibodies. The availability of the consensus sera will help evaluate and improve the EIA methods currently being used.

Antibodies, Antinuclear↗
PubMed2000

Phase III comparative study of vinorelbine combined with doxorubicin versus doxorubicin alone in disseminated metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group Study MA8.

PURPOSE: This phase III study was performed to determine the superiority of doxorubicin (DOX) and vinorelbine (VNB) (arm 1) versus DOX alone (arm 2) in metastatic breast cancer (MBC) for overall survival (OS), time to treatment failure (TTF), toxicity, and quality of life (QOL). PATIENTS AND METHODS: Three hundred three patients were randomized to DOX 50 mg/m(2) intravenously (IV) on day 1 and VNB 25 mg/m(2) IV on days 1 and 8 (arm 1) or DOX 70 mg/m(2) IV on day 1 (arm 2). Both regimens were given every 3 weeks until a cumulative DOX dose of 450 mg/m(2). After 16 of the first 65 randomized patients experienced febrile neutropenia (FN), the doses were reduced to DOX 40 mg/m(2) on day 1 and VNB 20 mg/m(2) on days 1 and 8 versus DOX 60 mg/m(2) on day 1. Eligible patients were vinca alkaloid and anthracycline naive. Chemotherapy was first-line or second-line for MBC. RESULTS: Three patients were ineligible. Thus, 300 patients were assessable for toxicity and to determine time to disease progression (TTP), TTF, and OS. Two hundred eighty-nine patients were assessable for response, and 99 responders were assessable for response duration (RD). The response rates, QOL, and median RD, TTP, and TTF were not significantly different between the arms. Median OS was 13.8 months for arm 1 versus 14.4 months for arm 2 (P =.4). Grade 3 or 4 granulocytopenia was equivalent in both arms but more grade 3/4 neurotoxicity, mild venous toxicity, and FN were seen on arm 1. CONCLUSION: The survival with DOX and VNB is not superior to DOX alone in MBC.

Adult↗
PubMed2000

Melatonin administration can entrain the free-running circadian system of blind subjects.

Although melatonin treatment has been shown to phase shift human circadian rhythms, it still remains ambiguous as to whether exogenous melatonin can entrain a free-running circadian system. We have studied seven blind male subjects with no light perception who exhibited free-running urinary 6-sulphatoxymelatonin (aMT6s) and cortisol rhythms. In a single-blind design, five subjects received placebo or 5 mg melatonin p.o. daily at 2100 h for a full circadian cycle (35-71 days). The remaining two subjects also received melatonin (35-62 days) but not placebo. Urinary aMT6s and cortisol (n=7) and core body temperature (n=1) were used as phase markers to assess the effects of melatonin on the During melatonin treatment, four of the seven free-running subjects exhibited a shortening of their cortisol circadian period (tau). Three of these had taus which were statistically indistinguishable from entrainment. In contrast, the remaining three subjects continued to free-run during the melatonin treatment at a similar tau as prior to and following treatment. The efficacy of melatonin to entrain the free-running cortisol rhythms appeared to be dependent on the circadian phase at which the melatonin treatment commenced. These results show for the first time that daily melatonin administration can entrain free-running circadian rhythms in some blind subjects assessed using reliable physiological markers of the circadian system.

Adult↗
PubMed2000

[Fish hooks: an unusual and sharp foreign body in the hypopharynx].

Foreign bodies in the hypopharynx occur commonly. A myriad of objects have been observed. In this report we describe a case involving a fish hook in a 10-year-old girl. The presence of this uncommon, sharp-pointed object was disclosed by plain radiography. The child was hospitalized three days after ingestion. Two attempts to perform endoscopic retrieval failed. Open cervicotomy was undertaken and allowed successful removal. The authors discuss management of this special type of foreign body and review several other unusual case reports in the literature.

Child↗
PubMed2000

The epidemiology of major early adverse physiological events after surgery.

OBJECTIVE: To study the incidence of major post-operative adverse physiological events in a tertiary hospital. METHODS: Non-cardiac, surgical in-patients were studied for the first three post-operative days. Daily assessment was by patient visit, chart review and laboratory result analysis. Pre-determined diagnostic criteria for the identification of adverse physiological events were used. RESULTS: One hundred and seven patients were studied. The mean age was 61 +/- 20 years. Forty-four were female and 63 were male. Pre-operatively, 48 patients had one or more of 34 different co-morbidities. Forty three (40%) of the 107 patients had one or more major adverse physiological events. These events included hypotension 24 (22%), altered mental state 16 (15%), oliguria 9 (8.4%), abnormal heart rate 8 (7.5%) and abnormal respiratory rate 5 (4.7%). Morbidity associated with these events included respiratory failure 5 (4.7%), prolonged altered mental state 5, (4.7%), and septic shock 3 (2.8%). There were two deaths. Adverse physiological events were common in thoracic 5/9 (56%), neurosurgical 4/10 (40%) and vascular 8/13 (62%) patients. Prolonged altered mental state was most common among orthopaedic patients 5/22 (23%). Adverse physiological events were more frequent in the elderly than the young: 14/52 (27%) in those who were less than 65 years of age versus 29/55 (53%) in those who were 65 years and older (p < 0.025). There was a non-significant increase (p < 0.1) in adverse physiological events in patients having emergency surgery 16/28 (57%) compared with those having elective surgery 27/79 (34%). CONCLUSIONS: This study reveals a high incidence of post-operative adverse physiological events in surgical patients in a university teaching hospital and identifies several high-risk groups. Further studies are needed to define the clinical significance of these events, appropriate management and prognosis.

Journal Article↗
PubMed1999

Childhood pancreatitis.

Acute pancreatitis is a rare finding in childhood but probably more common than is generally realized. This condition should be considered in the evaluation of children with vomiting and abdominal pain, because it can cause significant morbidity and mortality. Clinical suspicion is required to make the diagnosis, especially when the serum amylase concentration is normal. Recurrent pancreatitis may be familial as a result of inherited biochemical or anatomic abnormalities. Patients with hereditary pancreatitis are at high risk for pancreatic cancer.

Acute Disease↗
PubMed1999

Measuring response in solid tumors: unidimensional versus bidimensional measurement.

BACKGROUND: Tumor shrinkage is a common end point used in screening new cytotoxic agents. The standard World Health Organization criterion for partial response is a 50% or more decrease in the sum of the products of two measurements (the maximum diameter of a tumor and the largest diameter perpendicular to this maximum diameter) of individual tumors. However, theoretically, the simple sum of the maximum diameters of individual tumors is more linearly related to cell kill than is the sum of the bidimensional products. It has been hypothesized that the calculation of bidimensional products is unnecessary, and a 30% decrease in the sum of maximum diameters of individual tumors (assuming spherical shape and equivalence to a 50% reduction in the sum of the bidimensional products) was proposed as a new criterion. We have applied the standard response and the new response criteria to the same data to determine whether the same number of responses in the same patients would result. METHODS: Data from 569 patients included in eight studies of a variety of cancers were reanalyzed. The two response criteria were separately applied, and the results were compared using the kappa statistic. The importance of confirmatory measurements and the frequency of nonspherical tumors were also examined. In addition, for a subset of 128 patients, a unidimensional criterion for disease progression (30% increase in the sum of maximum diameters) was applied and compared with the standard definition of a 25% increase in the sum of the bidimensional products. RESULTS: Agreement between the unidimensional and bidimensional criteria was generally found to be good. The kappa statistic for concordance for overall response was 0.95. CONCLUSION: We conclude that one dimensional measurement of tumor maximum diameter may be sufficient to assess change in solid tumors.

Disease Progression↗