Search PubMed⌕ Search

Biomedical subjects

M O'Brien

Publications and source records attributed to M O'Brien.

At least 145 records · Page 8Linked to original sources
PubMed1996

Mucosal regeneration during radiotherapy. Trans Tasman Radiation Oncology Group (TROG).

BACKGROUND AND PURPOSE: Regeneration of the aerodigestive mucosa is known to occur during conventionally fractionated radiotherapy. The circumstances surrounding its time of onset and magnitude are not well understood, however. MATERIAL AND METHODS: Mucosal reactions were observed in 100 patients undergoing conventionally fractionated treatment at 2 Gy/day over 7 weeks and 88 receiving accelerated treatment at 1.8 Gy twice daily over 3 1/2 weeks on the Trans Tasman Radiation Oncology Group head and neck cancer trials. Similar observations in 61 patients treated palliatively at dose rates between 0.8 and 240 Gy/h using ten 3.0-4.2 Gy fractions over 2 weeks are compared. RESULTS: Several findings emerged from these studies: 1. Reactions evolved more quickly at oropharyngeal sites than in the hypopharynx. 2. Reactions at both sites evolved more rapidly at greater rates of dose accumulation. 3. The timing of reactions suggested the presence of a strong regenerative mucosal response that started before the manifestation of "patchy' (grade II) mucosal reactions. 4. The regenerative response was strong enough to "make good' damage accumulated at a rate of 2 Gy/day in over a third of cases. 5. The linear quadratic model without time correction failed to provide an adequate prediction of the frequency or intensity of mucosal reactions produced by any of the regimes. A simple model of the regenerative response is presented. CONCLUSIONS: This study suggests that the timing and magnitude of the regenerative response vary between sites and individuals but are linked to the amount of epithelial cellular depletion occurring during treatment.

Head and Neck Neoplasms↗
PubMed1996

Hormone replacement therapy as treatment of breast cancer--a phase II study of Org OD 14 (tibilone).

Org OD 14 (tibilone) is a synthetic steroid, designed to combine the favourable effects of oestrogens, progestagens and androgens into a single substance for use as hormone replacement therapy (HRT). Given its antiovulatory properties, the ability to control menopausal symptoms and blocking action on progesterone receptors, Org OD 14 was considered as an agent with potential anti-cancer activity while at the same time helping existing menopausal symptoms. In this phase II study, 14 post-menopausal women with advanced or metastatic breast cancer, who had failed on tamoxifen, were treated with Org OD 14. The median duration of treatment was 12 weeks and all patients stopped because of progressive disease with or without toxicity. Vaginal bleeding occurred in four patients, three of whom had recently stopped tamoxifen. One response was seen: an 82-year-old patient had a partial response in an axillary soft tissue mass, improvement in liver function tests and an improvement in her performance status that lasted over 6 months. One patient with progressive disease on Org OD 14 improved on stopping the drug. In view of the vaginal bleeding, Org OD 14 should not be given to patients who have recently stopped tamoxifen.

Adult↗
PubMed1996

Child-rearing difficulties reported by parents of infants and toddlers.

Surveyed a nonclinical sample of 413 parents of infants and toddlers about child-rearing difficulties, child behavior problems, and their own needs for support. Despite their high educational and income level, the parents surveyed reported raising young children to be a difficult task. Most concerns centered on children's irritating but developmentally typical behavior such as whining, noncompliance with adult requests, and interruption of adult activities. Parental reports of difficulties were highest for parents with more than one child and when children were past their second birthday.

Adaptation, Psychological↗
PubMed1996

Incidence and severity of injuries resulting from amateur boxing in Ireland.

OBJECTIVE: To determine the incidence, pattern, and severity of injuries resulting from participation in amateur boxing. DESIGN: A prospective 5-month survey of injuries which occurred during competitive amateur boxing and training. SETTING: Amateur boxing competitions held in Dublin between November 1992 and March 1993, and the six largest amateur boxing clubs in Dublin. PARTICIPANTS: All the competitors in the tournaments and the > 16 year old members of the boxing clubs. INTERVENTIONS: Participation in competitive amateur bouts and/or boxing training. MAIN OUTCOME MEASURES: Incidence, pattern, and severity of injuries sustained in competition and training. RESULTS: The incidence of injuries in competition was 0.92 injuries per man-hour of play (or 0.7 injuries per boxer per year), while the incidence in training was 0.69 injuries per boxer per year. Cerebral injuries were reported only in competition, most of these being mild concussion. Hand, wrist and facial injuries were related to direct impact and occurred more frequently in competition than training, while injuries to other body parts were predominantly chronic and training-associated. Shoulder and knee injuries were the most debilitating injuries seen. CONCLUSIONS: The yearly risk of injury resulting from participation in amateur boxing is relatively low when compared with other sports. Cerebral injuries, which occur almost exclusively in competition, are predominantly mild concussions.

Adolescent↗
PubMed1996

Low dose rate teletherapy: updated tumour response.

This report presents an update of tumour response experience in patients with locally advanced head and neck cancer treated on the low dose rate teletherapy project at the Mater Misericordiae Hospital, Newcastle. Long-term progression-free survival figures are disappointing in all dose rate/total dose groupings and offer little encouragement that an improvement in therapeutic ratio can be achieved for head and neck cancer patients using teletherapy apparatus adjusted to treat at low and intermediate dose rates.

Cesium Radioisotopes↗
PubMed1996

Role of the lactate transporter (MCT1) in skeletal muscles.

We used an antibody, constructed against the monocarboxylate transporter 1 (MCT1) protein (L. Carpenter, R. C. Poole, and A. P. Halestrap. Biochim. Biophys. Acta 1279: 157-165, 1996), to study the expression and role of MCT1 in rat skeletal muscles. MCT1 was higher in red than in white muscles (P < 0.05) and was highly correlated with the oxidative fiber content (%slow-twitch oxidative + %fast-twitch oxidative glycolytic) of skeletal muscles (r = 0.91). MCT1 was highly related to lactate uptake in skeletal muscles (r = 0.90). Total lactate dehydrogenase (LDH) activity, an index of glycolysis, was negatively correlated with MCT1 in rat muscles (r = -0.80). MCT1 was also strongly correlated with the heart-type forms of LDH (LDH-1 vs. MCT1, r = 0.83; LDH-2 vs. MCT1, r = 0.89). There was no relationship between MCT1 and the muscle form of LDH (LDH-5; P > 0.05). MCT1 was highly correlated with citrate synthase activity, a marker of the oxidative capacity of muscle (r = 0.82). Therefore, MCT1 may have kinetics that favor the uptake of L-lactate into the muscle cell for oxidative metabolism, and MCT1 may be coordinately expressed with the heart forms of LDH and enzymes of oxidative metabolism.

Animals↗
PubMed1996

Measurement of dimeric inhibin B throughout the human menstrual cycle.

This report describes the development of a specific and sensitive assay for inhibin B and its application to the measurement of inhibin B concentrations in plasma during the human menstrual cycle. A monoclonal antibody raised against a synthetic peptide from the betaB-subunit was combined with an antibody to an inhibin alpha-subunit sequence in a double antibody enzyme-linked immunosorbent assay format. The validated assay had a limit of detection of 10 pg/mL and 0.5% cross-reactivity with inhibin A. Using this immunoassay, we found that the plasma concentration of inhibin B rose rapidly in the early follicular phase to a peak of 85.2 +/- 9.6 pg/mL on the day after the intercycle FSH rise, then fell progressively during the remainder of the follicular phase. Two days after the midcycle LH peak, there was a short lived peak in the inhibin B concentration (133.6 +/- 31.2 pg/mL), which then fell to a low concentration (<20 pg/mL) for the remainder of the luteal phase. In contrast, the inhibin A concentration was low in the early follicular phase, rose at ovulation, and was maximal during the midluteal phase. The concentration of inhibin B in individual follicular fluid samples was 20- to 200-fold higher than the concentration of inhibin A and was highest in follicular fluid samples from the early follicular phase. Inhibin B appears to be the predominant form of inhibin in the preovulatory follicle. The different patterns of circulating inhibin B and inhibin A concentrations observed during the human menstrual cycle suggest that these forms may have different physiological roles.

Adult↗
PubMed1996

Recombinant human insulin-like growth factor I increases insulin sensitivity and improves glycemic control in type II diabetes.

Insulin resistance is a major factor in the pathophysiology of type II diabetes and a major impediment to successful therapy. The identification of treatments that specifically target insulin resistance could improve diabetes management significantly. Since IGFs exert insulin-like actions and increase insulin sensitivity when administered at supraphysiological doses, we determined the effect of 6 weeks of recombinant human IGF-I (rhIGF-I) administration on insulin resistance and glycemic control in obese insulin-resistant patients with type II diabetes. A total of 12 patients with type II diabetes were recruited for the study. Subcutaneous administration of rhIGF-I (100 micrograms/kg b.i.d.) significantly lowered blood glucose. Fructosamine declined from 369 to 299 mumol/l by 3 weeks of administration and then declined further to 271 at the end of 5 weeks. Glycosylated hemoglobin, which was 10.4% pretreatment, declined to 8.1% at the end of therapy. Mean 24-h blood glucose during a modal day was 14.71 +/- 4.5 mmol/l pretreatment and declined to 9.1 +/- 3.21 mmol/l by the end of treatment. These improvements in glycemia were associated with a decrease in serum insulin levels. Mean insulin concentrations declined from 108.0 to 57.0 pmol/l during the modal day measurements and from 97.2 to 72.0 pmol/l during the mixed-meal tolerance test. Changes in glycemia were accompanied by a marked increase in insulin sensitivity. The insulin sensitivity index (SI) calculated from a frequently sampled intravenous glucose tolerance test (FSIVGTT) after the method of Bergman et al. (Bergman RN, Finegold DT, Ader M: Assessment of insulin sensitivity in vivo. Endocr Rev 6:45-86, 1985) increased 3.4-fold. Furthermore, the improvement in glycemic control was accompanied by a change in body composition with a 2.1% loss in body fat as calculated by dual energy x-ray absorptiometry without change in total body weight. Significant side effects were present in some subjects, although nine subjects were able to complete at least 4.5 weeks of the protocol and six subjects completed the entire 6 weeks. Supraphysiological IGF-I concentrations were maintained throughout the study, increasing from 206 micrograms/l in the control period to 849 micrograms/l at the end of 6 weeks of rhIGF-I treatment. The increase in IGF-I levels was accompanied by a significant increase in IGF binding protein-2 levels, a slight reduction in IGF binding protein-3 levels, and an increase in levels of IGF binding protein-1. In summary, IGF-I significantly lowered blood glucose as reflected by short-term and long-term indexes of glycemic control and increased insulin sensitivity. It remains to be determined whether a dosage can be administered that avoids significant side effects and still achieves reasonable glycemic control.

Adult↗
PubMed1995

Combined modality therapy for esophageal carcinoma: preliminary results from a large Australasian multicenter study.

PURPOSE: This report updates local control and survival experience and focuses on treatment toxicity in 294 patients with esophageal cancer who have been treated at six Australasian centers using three prospective unrandomized protocols that used concurrent radiation, cisplatin, and modest dose infusional fluorouracil. METHODS AND MATERIALS: Protocol 1--"definitive" chemoradiation. One hundred and thirty-seven patients have been treated with "definitive" radiation to 60 Gy in 6 weeks plus two courses of cisplatin (80 mg/m2) and infusional fluorouracil (800 mg/m2/day over 4 days) during the first and fourth weeks of radiation. Protocol 2--"preoperative" chemoradiation and surgery. Seventy-eight patients received chemoradiation using the same chemotherapy, but 30-35 Gy in 3-4 weeks prior to surgery. Protocol 3--"palliative" chemoradiation. Seventy-nine patients deemed incurable were treated "palliatively" with the same chemoradiation protocol without surgery. Follow-up ranges from 6 months to 7 years (mean 22 months) in live patients. RESULTS: Durable palliation of dysphagia in all three treatment groups has been reflected by encouraging 3-year survival expectations of 43.2 +/- 5% in definitively treated patients, 40.3 +/- 7.65% in surgically treated patients, and 8.5% +/- 3.9% in the palliatively treated patients. There are early indications that female patients have fared better than males. Toxicity levels were modest in all three groups. Following definitive treatment, severe myelotoxicity (World Health Organization grades 3 and 4) occurred in 19%, severe esophagitis (World Health Organization grade 3) in 11%, and moderate or severe benign stricture in 17%, depending upon age and sex of the patient (being worse in female patients). CONCLUSIONS: These studies demonstrate that the concurrent addition of modest dose cisplatin and infusional dose fluorouracil to radiation in the definitive, preoperative, and palliative settings contribute to high rates of durable dysphagia-free survival, with overall survival comparable to (and possibly better than) the chemoradiation arm of the recently reported Intergroup Study, but at the cost of less morbidity.

Adenocarcinoma↗
PubMed1995

Simultaneous adjuvant radiation therapy and chemotherapy in high-risk breast cancer--toxicity and dose modification: a Transtasman Radiation Oncology Group Multi-Institution study.

PURPOSE: To establish the toxicity profile of simultaneously administered postoperative radiation therapy and CMF chemotherapy as a prelude to a randomized controlled study addressing the sequencing of the two modalities. METHODS AND MATERIALS: One hundred and thirty eight breast cancer patients at high risk of locoregional, as well as systemic relapse, who were referred to three centers in Australia and New Zealand were treated with postoperative radiation therapy and chemotherapy simultaneously. Acute toxicity and dose modifications in these patients were compared with 83 patients treated over the same time frame with chemotherapy alone. In a separate study the long-term radiation and surgical effects in 24 patients treated simultaneously with radiation therapy and chemotherapy at Newcastle (Australia) following conservative surgery were compared with 23 matched patients treated at Newcastle with radiation therapy alone. RESULTS: Myelotoxicity was increased in patients treated simultaneously with radiation therapy and chemotherapy. The effect was not great, but may have contributed to chemotherapy dose reductions. Lymphopenia was observed to be the largest factor in total white cell depressions caused by the simultaneous administration of radiation therapy. Postsurgical appearances were found to so dominate long-term treatment effects on the treated breast that the effect of radiation therapy dose and additional chemotherapy was difficult to detect. CONCLUSION: Studies addressing the sequencing of radiation therapy and chemotherapy will necessarily be large because adverse effects from administering the two modalities simultaneously are not great. The present study has endorsed the importance in future studies of stratification according to the extent and type of surgery and adherence to a single strict policy of chemotherapy dose modification.

Adult↗
PubMed1995

The herbicide dicamba (2-methoxy-3,6-dichlorobenzoic acid) is a peroxisome proliferator in rats.

The widely used broad leaf herbicide, dicamba, or Banvel, is similar in structure to xenobiotics which induce hepatic drug metabolism or proliferation of hepatic peroxisomes in rodents. The ability of xenobiotics to effect these hepatic changes often portends their positive outcomes in chronic bioassays. Dicamba's ability to induce hepatomegaly and peroxisome proliferation was studied in male and female Sprague-Dawley rats. Rats were placed on feed containing 0, 0.001, 0.01, 0.1, or 1% dicamba or 0.01% ciprofibrate for 3 weeks. Dicamba had no effect on relative liver weights or feed efficiency in either female or male rats at all doses tested. Dicamba, however, caused a statistically significant increase in peroxisomal beta-oxidation activity in liver homogenates from rats of both sexes fed 1% dicamba. Fatty acyl CoA-oxidase activity was increased in male rats fed 1% dicamba. A protein of M(r) 80 kDa was visible when liver homogenates of female or male rats fed 1% dicamba were subjected to SDS-PAGE. Lauric acid hydroxylase activity and CYP4A-reactive protein were increased in microsomes from male rats fed the highest level of dicamba. Moreover, dicamba was observed to transcriptionally upregulate the peroxisome proliferator-activated receptor (PPAR), a peroxisome proliferator sensitive receptor previously shown to be linked to the transcriptional regulation of a variety of peroxisome-specific enzymes. These studies show that dicamba is a peroxisome proliferator in rats. Although dicamba was not an efficacious inducer of peroxisomal enzymes in these rats, dicamba's ability to transcriptionally activate the PPAR and induce peroxisomal and related enzymes must be considered in the safety evaluation of this herbicide.

Acyl-CoA Oxidase↗
PubMed1995

Meralgia paraesthetica following laparoscopic inguinal hernia repair. An anatomical analysis.

Entrapment of the lateral cutaneous nerve of the thigh (LCNT) is a recognized complication of laparoscopic hernia repair. In our first 10 patients in a series of 30 laparoscopic herniorrhaphies we encountered two cases of meralgia paraesthetica, leading us to review our surgical technique and analyze the local anatomy in 20 LCNT cadaver dissections. The distances of the LCNT from fixed anatomical points were analyzed and safe margins of mesh placement at laparoscopic herniorrhaphy were defined.

Adolescent↗
PubMed1995

In vitro maturation and fertilization of oocytes isolated from aged mice: a strategy to rescue valuable genetic resources.

PURPOSE: This project was to determine whether oocytes isolated from virgin aged mice, up to 18 months old, are competent to undergo cytoplasmic maturation in vitro and undergo fertilization and embryonic development. If so, oocyte maturation in vitro could be used as a strategy to rescue valuable genetic resources. RESULTS: Although the number of oocytes recovered from mice was greatly reduced with increasing age, the percentage of oocytes that underwent fertilization, cleavage, and development to the blastocyst stage was essentially unchanged up to 18 months of age. The success of cleavage to the two-cell stage was greater after maturation in vitro (81%) than gonadotropin-induced maturation in vivo (55%). About 20% (20/106) of the embryos derived from oocytes isolated from 18-month-old mice developed to term after embryo transfer. CONCLUSION: Oocytes from virgin aged mice undergo normal cytoplasmic maturation in vitro. Higher percentages of oocytes from aged mice cleave to the two-cell stage after spontaneous maturation in vitro than after gonadotropin-induced maturation in vivo. Therefore, in vitro maturation and fertilization of oocytes could be used to rescue valuable genetic resources that might otherwise be lost because of age-related infertility.

Aging↗
PubMed1995

Factors influencing the degree of erythematous skin reactions in humans.

Dose-response relationships have been studied using an ordinal visual scale and reflectance spectrophotometry data from 123 treatment sites on 110 patients treated with 10 dose fractions over 12-14 days. Dose rates varied between 3 and 240 Gy/h and total doses of between 25 and 41 Gy were given using teletherapy apparatus. We found qualitative scoring of erythematous skin reactions to be subject to considerable inter- and intra-observer variation. Reflectance spectrophotometry provided more reproducible information, some of which was undetectable by naked eye. Baseline erythema readings were significantly higher in male patients and at anatomical sites of previous heavy UV exposure. In addition, a pronounced decline in erythema readings during the second week of therapy and 'reciprocal vicinity' (abscopal) effects adjacent to the field, undetected by the eye, were observed in a subset of patients. Meaningful dose-response relationships could be derived only from reflectance data with peak change from the pretreatment baseline measure providing the best discrimination. Peak erythema measures following treatment were found to depend on the age and gender of the patient as well as the treatment site and its baseline erythema measurement. This was independent of the total dose administered or the instantaneous dose rate at which it was delivered. The rate of erythema development was also dose rate dependent but only weakly dependent on the biological dose intensity (Gy equiv./day) of the treatment course. The data raise the question of whether irradiation-induced erythema is exclusively a secondary phenomenon occurring as a result of basal cell killing. The short repair half time value of 0.06 h obtained by direct analysis is perplexing and may reflect a dose rate-dependent physiological vasodilatory response to irradiation and/or a multi-component cellular repair process.

Aged↗
PubMed1995

Insulin-like growth factor I (rhIGF-I) as a therapeutic agent for hyperinsulinemic insulin-resistant diabetes mellitus.

Insulin resistance is one of the major underlying abnormalities in NIDDM, however, its pathophysiologic mechanisms are not well understood. Many clues about the mechanisms of insulin action have come from patients with the most severe forms of insulin resistance, including those with genetic abnormalities in the insulin signal transduction cascade. We used rhIGF-I as a probe to differentiate insulin and IGF-I action and to study the therapeutic potential of IGF in states of insulin resistance. To date, we have studied six subjects with varying phenotypes of severe insulin resistance but without mutations in the insulin receptor itself. All subjects underwent baseline physiologic monitoring to quantitate carbohydrate tolerance, insulin secretion, and insulin action prior to receiving rhIGF-I at 100 micrograms/kg body wt s.c. bid for 1 month with interval testing of glycemic control and insulin sensitivity. None of the six subjects noted significant side effects from the rhIGF-I. Four of the six subjects had overt diabetes during control testing; three of these subjects demonstrated normalization of fasting and postprandial blood glucose concentrations during rhIGF-I administration on no other therapy. In the fourth patient, insulin requirements and fasting hypertriglyceridemia decreased without improvement in glycemic control. The two subjects with normal glucose tolerance (two sisters with congenital lipodystrophy) maintained normal glucose tolerance at dramatically lower insulin levels and had a dramatic reduction in triglyceride levels. The efficacy of IGF-I continued to increase over the duration of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1995

IntroStat: a hypertext-based design for an electronic textbook to introduce biomedical statistics.

A hypertext-based system called IntroStat has been developed to introduce fundamental methods of biomedical statistics. The system has been developed on a Macintosh II using HyperCard. It is written mainly in Hypertalk, a scripting language of HyperCard. Being an electronic textbook of probability and statistics, the system features computational capabilities. At the end of the sections describing basic methods of statistics, pages are provided where a user may enter data and try the methods right there. Some means for branching are provided for easy access to a page of interest, including branching by contents, by index, and by keyword reference. The system design is proposed as a model of an electronic textbook for biomedical statistics.

Biometry↗