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Biomedical subjects

M Hogg

Publications and source records attributed to M Hogg.

18 recordsLinked to original sources
PubMed2004

Phase I dose-escalation trial of irinotecan with continuous infusion 5-FU first line, in metastatic colorectal cancer.

This single-centre phase I trial was designed to determine the maximum tolerated dose of irinotecan and the recommended dose to use in combination with a fixed dose of 5-fluorouracil (5-FU) administered as a protracted venous infusion, for the first-line treatment of metastatic colorectal cancer (CRC). Tolerability and efficacy were secondary end points. In all, 22 patients, median age 57 years, were treated with escalating, weekly doses of irinotecan (50, 75, 100 and 85 mg m(-2)) in combination with 250 mg m(-2) 5-FU administered as a continuous infusion. All patients had measurable disease. The combination was well tolerated up to an irinotecan dose of 75 mg m(-2). However, three out of five patients at the 100 mg m(-2) irinotecan dose level had their dose reduced due to multiple grade 2 toxicities, and eventually one patient stopped treatment due to grade 3 diarrhoea and multiple grade 2 toxicities. Subsequent patients were recruited at an irinotecan dose level of 85 mg m(-2). The overall response rate was 55%, comprising one complete and 11 partial responses (PRs). Six patients also achieved sustained stable disease (SD), giving a clinical benefit (complete response/PR/SD) response of 82%. The median duration of response was 238 days (8.5 months) and median time to progression was 224 days (8.0 months). Two patients who achieved PRs underwent partial hepatectomies. Thus, irinotecan (85 mg m(-2)) combined with a continuous infusion of 5-FU (250 mg m(-2)) is an active and well-tolerated regimen for the treatment of metastatic CRC. It represents an effective treatment for patients who require close supervision and support, throughout their initial exposure to chemotherapy for this disease, and this dose combination was recommended for an ongoing phase II study.

Adult↗
PubMed2004

Likelihood ratio for trisomy 21 in fetuses with absent nasal bone at the 11-14-week scan.

OBJECTIVE: To update the likelihood ratio for trisomy 21 in fetuses with absent nasal bone at the 11-14-week scan. METHODS: Ultrasound examination of the fetal profile was carried out and the presence or absence of the nasal bone was noted immediately before karyotyping in 5918 fetuses at 11 to 13+6 weeks. Logistic regression analysis was used to examine the effect of maternal ethnic origin and fetal crown-rump length (CRL) and nuchal translucency (NT) on the incidence of absent nasal bone in the chromosomally normal and trisomy 21 fetuses. RESULTS: The fetal profile was successfully examined in 5851 (98.9%) cases. In 5223/5851 cases the fetal karyotype was normal and in 628 cases it was abnormal. In the chromosomally normal group the incidence of absent nasal bone was related first to the ethnic origin of the mother, being 2.2% for Caucasians, 9.0% for Afro-Caribbeans and 5.0% for Asians; second to fetal CRL, being 4.7% for CRL of 45-54 mm, 3.4% for CRL of 55-64 mm, 1.4% for CRL of 65-74 mm and 1% for CRL of 75-84 mm; and third to NT, being 1.6% for NT < or = 95th centile, 2.7% for NT > 95th centile-3.4 mm, 5.4% for NT 3.5-4.4 mm, 6% for NT 4.5-5.4 mm and 15% for NT > or = 5.5 mm. In the chromosomally abnormal group there was absent nasal bone in 229/333 (68.8%) cases with trisomy 21 and in 95/295 (32.2%) cases with other chromosomal defects. Logistic regression analysis demonstrated that in the chromosomally normal fetuses significant independent prediction of the likelihood of absent nasal bone was provided by CRL, NT and Afro-Caribbean ethnic group, and in the trisomy 21 fetuses by CRL and NT. The likelihood ratio for trisomy 21 for absent nasal bone was derived by dividing the likelihood in trisomy 21 by that in normal fetuses. CONCLUSION: At the 11-14-week scan the incidence of absent nasal bone is related to the presence or absence of chromosomal defects, CRL, NT and ethnic origin.

Adolescent↗
PubMed2004

Patient characteristics and quality of life among a sample of Australian chronic pain clinic attendees.

BACKGROUND: Multidisciplinary chronic pain management programs have proliferated widely in recent decades. The clinical characteristics of patients attending these clinics are becoming the subject of increased research. Recent European data suggests that patients attending these clinics report very low quality of life. AIMS: The present study profiles an Australian population in terms of demographics, clinical characteristics and quality of life, as measured by the Short Form 36 Quality of Life Questionnaire (SF-36). METHODS: Data were collected prospectively from consecutive patients presenting to a multidisciplinary chronic pain clinic at a major Sydney metropolitan teaching-hospital. Cross-sectional analysis of demographic and clinical characteristics and quality of life were then undertaken. RESULTS: Descriptive analysis of demographics and clinical characteristics suggest a patient population group reporting significant pain severity and reduced quality of life. The comparison of SF-36 domain scores between clinic patients and Australian norm values indicates a greatly reduced score on all SF-36 domains for clinic patients. Pain clinic patients reported the most profound effect upon quality of life in the role physical, physical function and social function domains of the SF-36. Stepwise multiple regression indicated impaired coping ability and depressive disability as the most significant correlates of low quality of life. CONCLUSION: Patients who attend chronic pain clinics are likely to report low quality of life with an inability to cope. These findings suggest that future intervention research should explore the impacts of behavioural and self-management interventions. Psychological distress and ability to cope could be used as indices of improvement.

Adult↗
PubMed2001

Hyaluronan enters keratinocytes by a novel endocytic route for catabolism.

Hyaluronan synthesized in the epidermis has an exceptionally short half-life, indicative of its catabolism by epidermal keratinocytes. An intracellular pool of endogenously synthesized hyaluronan, from 1 to 20 fg/cell, inversely related to cell density, was observed in cultured rat epidermal keratinocytes. More than 80% of the intracellular hyaluronan was small (<90 kDa). Approximately 25% of newly synthesized hyaluronan was endocytosed by the keratinocytes and had a half-life of 2-3 h. A biotinylated aggrecan G(1) domain/link protein probe demonstrated hyaluronan in small vesicles of approximately 100 nm diameter close to the plasma membrane, and in large vesicles and multivesicular bodies up to 1300 nm diameter around the nucleus. Hyaluronan did not co-localize with markers of lysosomes. However, inhibition of lysosomal acidification with NH(4)Cl or chloroquine, or treating the cells with the hyaluronidase inhibitor apigenin increased intracellular hyaluronan staining, suggesting that it resided in prelysosomal endosomes. Competitive displacement of hyaluronan from surface receptors using hyaluronan decasaccharides, resulted in a rapid disappearance of this endosomal hyaluronan (t(12) approximately 5 min), indicating its transitory nature. The ultrastructure of the hyaluronan-containing vesicles, co-localization with marker proteins for different vesicle types, and application of specific uptake inhibitors demonstrated that the formation of hyaluronan-containing vesicles did not involve clathrin-coated pits or caveolae. Treatment of rat epidermal keratinocytes with the OX50 monoclonal antibody against the hyaluronan receptor CD44 increased endosomal hyaluronan. However, no CD44-hyaluronan co-localization was observed intracellularly unless endosomal trafficking was retarded by monensin, or cultivation at 20 degrees C, suggesting CD44 recycling. Rat epidermal keratinocytes thus internalize a large proportion of their newly synthesized hyaluronan into non-clathrin-coated endosomes in a receptor mediated way, and rapidly transport it to slower degradation in the endosomal/lysosomal system.

Animals↗
PubMed2000

A preformed basal lamina alters the metabolism and distribution of hyaluronan in epidermal keratinocyte "organotypic" cultures grown on collagen matrices.

A rat epidermal keratinocyte (REK) line which exhibits histodifferentiation nearly identical to the native epidermis when cultured at an air-liquid interface was used to study the metabolism of hyaluronan, the major intercellular macromolecule present in basal and spinous cell layers. Two different support matrices were used: reconstituted collagen fibrils with and without a covering basal lamina previously deposited by canine kidney cells. REKs formed a stratified squamous, keratinized epithelium on both support matrices. Hyaluronan and its receptor, CD44, colocalized in the basal and spinous layers similar to their distribution in the native epidermis. Most (approximately 75%) of the hyaluronan was retained in the epithelium when a basal lamina was present while most (approximately 80%) diffused out of the epithelium in its absence. While REKs on the two matrices synthesized hyaluronan at essentially the same rate, catabolism of this macromolecule was much higher in the epithelium on the basal lamina (half-life approximately 1 day, similar to its half-life in native human epidermis). The formation of a true epidermal compartment in culture bounded by the cornified layer on the surface and the basal lamina subjacent to the basal cells provides a good model within which to study epidermal metabolism.

Animals↗
PubMed2000

Angiogenic and immune parameters during recombinant interferon-alpha2b adjuvant treatment in patients with melanoma.

As an adjuvant therapy for patients with high risk of recurrent melanoma, high-dose interferon (IFN)-alpha2b therapy has been shown to have some efficacy. We examined 22 patients with resected melanoma who were treated with repeated injections of recombinant IFN-alpha2b during the treatment. Both angiogenic and immune parameters were measured. White blood cells (WBCs) and lymphocyte numbers, lymphocyte subpopulations, serum concentrations of IFN-alpha and anti-IFN-alpha antibodies, and the serum vascular endothelial growth factor (VEGF), interleukin (IL)-8, and basis fibroblast growth factor (bFGF) concentrations were determined over time in resected, recurrence-free patients with American Joint Committee on Cancer (AJCC) stage III melanoma with one or less (LN+ < or = 1, n = 7) or more than one (LN+ > 1, n = 8) lymph nodes involved, and AJCC stage IV resected disease (n = 7). Follow-up and recurrence-free intervals were longer in stage III (LN+ < or = 1) patients compared with stage IV patients (P < 0.05). The number of WBCs and lymphocytes decreased during the treatment for all patient groups (P < 0.001). In addition, percentages of CD8 and CD20 were higher in stage IV patients than in stage III (LN+ > 1) and stage III (LN+ < or = 1) patients at the beginning of therapy (P < 0.05). A significant increase in the percentage of CD20+ cells, mostly B lymphocytes, was observed in the stage III (LN+ > 1) and stage III (LN+ < or = 1) patients over time but not in stage IV patients (P < 0.001). Low IL-8 and bFGF concentrations at the beginning of therapy were associated with significantly longer recurrence-free survival (P < 0.05). These results warrant a larger trial to determine if the differences observed in patients before treatment can provide prognostic markers in patients receiving IFN-alpha2b therapy.

Adjuvants, Immunologic↗
PubMed1999

The case-based Internet textbook ODITEB for multi-modal diagnosis of tumors--development, features and first experiences.

Internet technologies offer the chance to build high-quality learning media for the education in medicine. In particular, the teaching of diagnostics with medical imaging can be supported by the excellent visualization and interaction capabilities. In cooperation with three radiological departments at German universities in Munich, Erlangen and Würzburg the distributed case-based Internet textbook ODITEB for tumor diagnosis of the GI-tract, liver, pancreas and thorax has been developed. It offers a growing collection of didactically prepared cases located on servers at the provider sites Munich, Erlangen and Würzburg, functionality similar to a real CT console, original DICOM data, X-rays and endoscopic and endosonographic videos, and expert-guided tours through the cases. In a first evaluation in summer 1998, 32 medical students graded the application with 1.9 ('good') on a scale from 1 ('very good') to 5 ('very bad').

Computer-Assisted Instruction↗
PubMed1998

Concepts of a Web-based open distributed textbook for the multimodal diagnostics of gastrointestinal tumours with MRI, CT and video-endoscopy addressing students of medicine and students of medical informatics as two different target groups.

Multimodal diagnostics of gastrointestinal tumours with MRI, CT and video-endoscopy is a rapidly changing domain. The education at our universities should overcome the obstacles of traditional learning based on paper media and oral lectures with retention rates of 10-30% only. The paper presents the objectives and the results of the design phase of the project ODITEB1-Open Distributed TExt Book, for Computer-Assisted Instruction in the domain mentioned above. The main objective is to produce an electronic interactive textbook in order to shift education to more efficient learning settings with higher retention rates. The main concepts are 1) three-layer architecture (dynamic case layer, intermediate query layer, static instruction layer) 2) case pool distribution 3) active learners experience (interactive exploration of original image data).

Computer-Assisted Instruction↗
PubMed1991

Chloride influx in human leucocytes: a triple-isotope technique for the assessment of chloride transporters.

1. A novel triple-isotope method using 3H2O, [14C]-sucrose and 36Cl- for measuring initial Cl- uptake rates in human leucocytes that had been preincubated in 10% (v/v) autologous serum is described. 2. There was a marked dependence of Cl- influx on intracellular pH, the flux at an intracellular pH of 7.20 being about 11.2% of that at an intracellular pH of 7.56. 3. This Cl- influx was inhibited by 4,4-di-isothiocyanatostilbene-2,2-disulphonic acid in a dose-dependent manner. Half-maximal inhibition by 4,4-di-isothiocyanatostilbene-2,2-disulphonic acid at an internal pH of 7.56 in the presence or absence of HCO3- was 0.30 or 0.35 mmol/l, respectively. 4. Depletion of intracellular Cl- resulted in a 70.7% decrease in Cl- influx, whereas depletion of cellular ATP led to a 37.7% decrease in Cl- influx. 5. The phorbol ester 12-O-tetradecanoyl phorbol acetate at a concentration of 0.1 mumol/l reduced Cl-influx, especially the 4,4-di-isothiocyanatostilbene-2,2-disulphonic acid-sensitive component. This effect was independent of intracellular pH changes or Na+/H+ antiport activity.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1988

Universal precautions: employee resistance and strategies for planned organizational change.

Health care organizations have been strongly encouraged to design and implement procedures to prevent the spread of HIV/AIDS in the workplace. The procedures will have a dramatic impact on the work habits of health care workers and may even challenge some dominant health care values. Therefore, precautionary procedures are likely to meet with mixed reactions and, perhaps, outright resistance from health care workers. This article identifies some plausible causes for employee resistance to precautionary procedures. After describing the dilemma in terms of competing values and conflicting objectives, some practical managerial strategies for reconciling differences and securing broad-based commitment to preventive policies and procedures are proposed.

Acquired Immunodeficiency Syndrome↗
PubMed1975

Maternal arterial oxygen tension during intermittent inhalation analgesia.

In mothers nursed in a semi-recumbent position, arterial oxygen tension was measured at the beginning and END OF AN an intermittent period of inhalation, Lasting for six contractions, during the first stage of labour. Ten mothers had methoxyflurane 0.35 per cent and air, followed by methoxyflurane 0.35 per cent with approximately 50 per cent oxygen. Another 10 mothers had 50 per cent nitrous oxide and 50 per cent oxygen (Entonox). The mean values of PaO2 at the beginning of periods of inhalation in those who received methoxyflurane in air, methoxyflurane in 50 per cent oxygen, and nitrous oxide in oxygen were 109, 120 and 106 mm Hg respectively. The mean increases in PaO2 by the ends of periods of inhalation were 18, 43 and 63 mm Hg respectively. On average, increasing the inspired concentration of oxygen to 50 per cent significantly and substantially increased maternal PsO2 with both agents by the emd pf inhalation. There would therefore be some increase in available oxygen during the phase of higher blood flow following a uterine contraction. However, the lowest maternal PaO2 measured was 72 mm Hg; therefore additional oxygen is unlikely to offer much advantage except in patients with respiratory or cardiac deficiencies. In the intervals between inhalations of the analgesic mixture the PaO2 decreased to about the level found during air breathing. Consequently it would be necessary to breather additional oxygen continuously, between as well as during contractions, to ensure an increased maternal PaO2 throughout labour.

Anesthesia, Inhalation↗