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Biomedical subjects

A O'Connor

Publications and source records attributed to A O'Connor.

At least 19 recordsLinked to original sources

Secondary lactose intolerance in a neonatal goat.

A 2-week-old Toggenburg kid was evaluated for persistent diarrhea and poor body condition. The herd had high morbidity and mortality associated with diarrhea in neonatal kids. Lactose intolerance was diagnosed on the basis of results of a lactose tolerance test and glucose absorption test. Clinically normal herdmates were used as control animals. The kid responded to lactase supplementation. Cryptosporidium organisms were detected in feces of several affected kids during episodes of acute diarrhea. Lactose intolerance was presumed to have developed secondary to intestinal cryptosporidiosis.

Animals↗

"Herbal Ecstasy": a case series of adverse reactions.

AIMS: To report five cases of adverse effects associated with the ingestion of "Herbal Ecstasy" tablets and discuss possible mechanisms of toxicity. METHOD: Composition of the "Herbal Ecstasy" tablets was determined by discussions with distributors and with MEDSAFE: Reference to relevant texts and an internet and Medline literature search was used to identify articles of interest RESULTS: Three patients complained of minor symptoms such as perceptual disturbances, anorexia, inability to sleep, dizziness, palpitations and paresthesia. A fourth patient presented with palpitations and ventricular bigeminy, and a fifth patient presented with headache, vomiting, and a hypertensive crisis. Different brands of "Herbal Ecstasy" have different compositions, some containing caffeine and kava, and one contained ephedrine. CONCLUSION: These five patients presented with adverse reactions to "Herbal Ecstasy" ranging from minor to major. Knowledge of the possible mechanisms of toxicity will help plan therapy in cases of major toxicity.

Adolescent↗

Comparison of telomerase levels before and after differentiation of two cell lines of human neuroblastoma.

BACKGROUND: Telomerase is the enzyme that is responsible for maintaining telomere length in human germ cells, tumor cells, and immortalized cells. Its specific role in the immortilization process is unknown. This study was performed to determined whether the level of telomerase activity in human neuroblastoma cell lines correlated with their level of differentiation. We proposed that as neuroblastoma cells differentiated into more mature or benign cells, the levels of telomerase expression would decrease. MATERIALS AND METHODS: Two human neuroblastoma cells lines, SK-N-AS and SK-N-DZ, were differentiated using retinoic acid. These cells were assayed for telomerase activity by the telomere repeat amplification protocol (TRAP) before, during, and after treatment with retinoic acid for 8 days. Untreated cells were used for control and were compared to the retinoic acid-treated cells. Differentiation of the cell lines was confirmed by assaying expression of ret mRNA using the reverse-transcriptase polymerase chain reaction (RT-PCR) and gel electrophoresis of the radiolabeled products. RESULTS: No statistical difference in telomerase activity was noted between control and treated groups. CONCLUSIONS: While telomerase activity has been shown by others to correlate with tumor aggressiveness in human neuroblastoma cells, the mechanism that is involved appears to be separate from cellular differentiation.

Cell Differentiation↗

The periodontal abscess (II). Short-term clinical and microbiological efficacy of 2 systemic antibiotic regimes.

BACKGROUND/AIMS: The aim of this short-term open parallel longitudinal clinical study was to compare the clinical and microbiological efficacy of 2 different antibiotic regimes in the treatment of acute periodontal abscesses. METHOD: After patient selection, a clinical examination was carried out recording the following variables: pain, edema, redness, swelling, bleeding on probing, suppuration, tooth mobility, lymphadenopathy, and probing pocket depth. Microbiological samples were taken from the lesion and the patient was randomly assigned to one of two antibiotic regimes: azithromycin or amoxicillin/clavulanate. Clinical variables were recorded, and microbiological samples were taken, at 3-5 days, 10-12 days and 30 days. Additional mechanical treatment (debridement and scaling) was performed in the third visit (10-12 days). Blood and urine samples were collected at baseline and after 10-12 days. Microbiological samples were processed by anaerobic culturing, and isolated periodontal pathogens were tested for antibiotic susceptibility by means of the spiral gradient endpoint methodology. RESULTS: 15 patients took azithromycin, and 14 amoxicillin/clavulanate. Subjective clinical variables demonstrated statistically significant improvements with both antibiotic regimes, which lasted for at least 1 month (p<0.01). Objective clinical variables also showed clear improvements, being statistically significant after 30 days with probing pocket depth in the azithromycin group (p<0.01). Microbiologically, short-term reductions were detected with both antibiotics, however fast recolonization occurred after the third visit. No significant differences were found between both treatment regimes. Antibiotic susceptibilities demonstrated no resistances for amoxicillin/clavulanate, while 2-3 strains of each studied pathogen were resistant to azithromycin. CONCLUSIONS: However, both antibiotic regimes were effective in the short-term treatment of periodontal abscesses in periodontitis patients.

Acute Disease↗

Maternal serum total activin A and follistatin in pregnancy and parturition.

OBJECTIVE: To examine changes in maternal serum levels of activin A and follistatin during pregnancy and labour. DESIGN: In three cross sectional and three longitudinal studies venous blood was collected from women during pregnancy, spontaneous labour, labour induction and prior to elective caesarean section for the measurement of activin A and follistatin. SETTING: Monash Medical Centre, Clayton, Victoria, Australia. POPULATION: One hundred and twenty-three women participated in a cross sectional study in pregnancy, 18 women in two longitudinal pregnancy studies, 36 women in a cross sectional labour study, nine women in a longitudinal study of labour induction. Ten women undergoing elective caesarean section were also studied. METHODS: Activin A and follistatin were measured using two sensitive and specific enzyme-linked immunosorbent assays. RESULTS: In the cross sectional study of pregnancy, mean (SEM) maternal serum activin A and follistatin levels increased towards term (2.4 ng/mL (0.3) and 1.8 ng/mL (0.3) in first trimester to 18.9 ng/mL (3.8) and 5.3 ng/mL (0.9) at term, respectively), but the longitudinal study revealed that levels plateau in the last three weeks of pregnancy (16.0 ng/mL (2.6) and 6.2 ng/mL (1.4) at 37 weeks and 16.6 ng/mL (3.5) and 6.2 ng/mL (0.5) before labour for activin A and follistatin, respectively). There was no difference in levels of activin A and follistatin between women delivered by caesarean section and labouring women at term (14.9 ng/mL (2.8) vs 11.0 ng/mL (0.93) and 5.95 ng/mL (0.67) vs 5.71 ng/mL (0.63), respectively) and levels of both proteins did not alter throughout spontaneous or induced labour. CONCLUSIONS: We believe that these data argue against activin A playing an acute role in the initiation or regulation of human parturition.

Activins↗

A comparison of the efficacy and safety of morphine and pethidine as analgesia for suspected renal colic in the emergency setting.

OBJECTIVES: The aim of this study was to compare morphine and pethidine in patients with clinically suspected renal colic with regard to analgesic efficacy, patient satisfaction and side effects. METHODS: double blinded, randomised controlled trial. RESULTS: There was no significant difference between morphine and pethidine with respect to any of the parameters measured. CONCLUSION: Because of the well known adverse effects that may be associated with pethidine use, the authors recommend that morphine should be the preferred agent in suspected renal colic, when an opioid analgesic is to be used.

Adolescent↗

Canadian oncologists and clinical practice guidelines: a national survey of attitudes and reported use. Provincial Lung Disease Site Group of Cancer Care Ontario.

PURPOSE: To determine (1) Canadian oncologists' attitudes toward practice guidelines, (2) oncologists' self-reported use of practice guidelines and, (3) physicians' characteristics and attitudes associated with self-reported use of practice guidelines. PARTICIPANTS AND METHODS: A cross-sectional, self-administered postal survey was administered to Canadian oncologists. Main outcome measures were level of agreement with 8 descriptive statements about guidelines, score on the attitudinal scale of the guideline of Tunis et al., and physicians' stated use of guideline. chi(2) and logistic regression procedures were used to explore the relationship between physician characteristics and use of guidelines. RESULTS: Over 80% of respondents agreed that they were good educational tools, convenient sources of advice, intended to improve quality of care; over 40% agreed that they were unbiased syntheses of expert opinion. Conversely, 42, 26, 20 and 16% felt they were intended to cut costs, were oversimplified cookbook medicine, were too rigid to apply to individual patients, and a challenge to physicians' authority, respectively. Forty-one percent reported using practice guidelines routinely or most of the time. Use was associated with positive attitudes about guidelines, receiving medical school training abroad and being a radiation oncologist. CONCLUSION: Canadian oncologists were quite positive about practice guidelines and reported using them frequently. Our results suggest that use of guidelines by oncologists may be related to attitudes about guidelines in general, specialty within oncology and country of medical school training.

Adult↗

Cost containment in sports rehabilitation.

Defining high-quality care and cost-effectiveness is not an easy task. In this article, the authors describe several strategies that have practical applicability for the clinician treating patients with sports-related injuries. Integration of some of these strategies may allow the more quality-based, cost-efficient use of available resources in sports rehabilitation.

Athletic Injuries↗

Intubation and mechanical ventilation for COPD: development of an instrument to elicit patient preferences.

BACKGROUND: Whether to simply provide palliative care or to intubate and use mechanical ventilation (MV) in a patient with severe COPD in acute respiratory failure is a difficult decision. The outcome of MV cannot be accurately predicted. Some patients cannot be weaned from the ventilator; those who are weaned often return to chronic severe respiratory disability. It is important that patients participate in this decision, but assistance is required. To address these issues, we developed and pilot-tested an aid to assist patients with MV decisions. METHODS: A scenario-based decision aid was developed consisting of an audiocassette and a booklet describing intubation and MV and its possible outcomes. We used a probability tradeoff technique to elicit the patients' preferences and a decisional conflict scale to evaluate satisfaction. RESULTS: With the assistance of the decision aid, all patients (10 men and 10 women) reached a decision. Two men and all 10 women declined MV. Mean decisional conflict was low (2.2 of a possible 5; SD, 0.9). At 1 year, only two patients (11%) had changed their decision. The agreement between physicians and patients was 65%; between next-of-kin and patients, there was uniform disagreement. CONCLUSION: With the decision aid, stable decisions were made with satisfaction and confidence. Proxy decisions were incongruent, especially when made by family members. The strong gender effect should be further investigated. We suggest that the COPD decision aid be further tested in a community clinical setting.

Acute Disease↗

Photoprotection by topical DNA repair enzymes: molecular correlates of clinical studies.

A new approach to photoprotection is to repair DNA damage after UV exposure. This can be accomplished by delivery of a DNA repair enzyme with specificity to UV-induced cyclobutane pyrimidine dimers into skin by means of specially engineered liposomes. Treatment of DNA-repair-deficient xeroderma pigmentosum patients or skin cancer patients with T4N5 liposome lotion containing such DNA repair liposomes increases the removal of DNA damage in the first few hours after treatment. In these studies, a DNA repair effect was observed in some patients treated with heat-inactivated enzyme. Unexpectedly, it was discovered that the heat-inactivated T4 endonuclease V enzyme refolds and recovers enzymatic activity. These studies demonstrate that measurements of molecular changes induced by biological drugs are useful adjuvants to clinical studies.

Administration, Topical↗

Women's decisions about hormone replacement therapy after education and bone densitometry.

BACKGROUND: The decisions that postmenopausal women make about whether to start hormone replacement therapy may depend on the potential risks and benefits of such therapy as well as their risk for osteoporosis-related fractures. This study examined the decisions made by women at risk for osteoporosis-related fractures who were educated about hormone replacement therapy and who were given information about their bone mineral density. METHODS: The study employed a prospective cohort design. Thirty-seven post--menopausal women with risk factors for osteoporosis-related fractures were recruited from an orthopedic clinic at a teaching hospital in Hamilton, Ont. The women were given an education kit (consisting of an audio tape and a work-book) to clarify the benefits and risks of hormone replacement therapy. Two to 4 weeks later, densitometry of the hip and the lumbar spine was performed. A summary of the risks, the densitometry findings and decisions about hormone replacement therapy were given to the women's family physicians for follow-up. Outcome measures included decisions about hormone replacement therapy, as well as use of such therapy and other medications at 12 months. RESULTS: After the education component alone, 10 (27%) of the women requested hormone replacement therapy. After densitometry testing, 4 more requested hormone replacement therapy (for a total of 14 women [38%]). At 12 months, 2 (5%) of the women had been lost to follow-up. Of the remaining 35, 6 (17%) were receiving hormone replacement therapy, 7 (20%) were using bisphosphonates, and 24 (68%) were taking calcium supplements. INTERPRETATION: These preliminary findings suggest that the combination of education about hormone therapy and feedback about bone density is associated with an increase in the use of hormone replacement therapy and other preventive medications by women at risk for osteoporosis-related fractures. However, the observed increase was small and so the clinical significance must be confirmed and clarified.

Absorptiometry, Photon↗

HindIII liposomes suppress delayed-type hypersensitivity responses in vivo and induce epidermal IL-10 in vitro.

Considerable evidence suggests that ultraviolet-B (UV-B) radiation suppresses certain immune responses through the induction of cyclobutane pyrimidine dimers in DNA. To determine whether induction of other forms of DNA damage in the skin mimicked the immunosuppressive effects of UV-B radiation, we produced double-strand breaks in the DNA of epidermal cells with HindIII restriction endonuclease encapsulated in liposomes. Application of these liposomes, but not liposomes containing inactive HindIII or an irrelevant endonuclease, to the skin of C3H mice suppressed the induction of delayed-type hypersensitivity responses to Candida albicans and alloantigen and induced IL-10 production in the epidermis. Treatment of the Pam212 murine keratinocyte cell line with these liposomes in vitro induced immunosuppressive activity and IL-10 in culture supernatants. Unlike UV-B irradiation, however, HindIII in liposomes failed to induce suppressor T cell activity in vivo or in vitro. We conclude that double-strand breaks in DNA of epidermal cells can induce immunosuppression and up-regulate the production of immunomodulatory cytokines; however, either DNA damage alone does not account for all the immunosuppressive properties of UV-B irradiation, or cyclobutane pyrimidine dimers differ qualitatively from double-strand breaks in their biologic consequences. These studies raise the possibility that drugs causing DNA damage may induce cytokine dysregulation and immune suppression in addition to cytotoxicity.

Animals↗

High morbidity of enterostomy and its closure in premature infants with necrotizing enterocolitis.

OBJECTIVE: To review the morbidity and mortality among 68 premature infants treated with enterostomy for necrotizing enterocolitis. DESIGN: Data were collected retrospectively from hospital medical records to include the period between January 1, 1987, and September 30, 1997. SETTING: Tertiary care children's hospital. PATIENTS: A group of 68 infants aged 2 to 35 days (mean age, 12.5 days), weighing 1500 g or less, with necrotizing enterocolitis necessitating surgical enterostomy for treatment. INTERVENTIONS: Creation of any enterostomy during exploratory laparotomy for necrotizing enterocolitis and subsequent closure. MAIN OUTCOME MEASURES: Morbidity and mortality associated with infant enterostomy and its closure. RESULTS: Thirty-nine infants underwent ileostomy with mucous fistula, 16 underwent ileostomy with a Hartmann pouch, 7 had jejunostomy with mucous fistula, 2 had colostomy with mucous fistula, and 4 had colostomy with a Hartmann pouch. Eighteen (26%) of the 68 infants died in the postoperative period of sepsis (n = 10), continuing necrotizing enterocolitis (n = 5), or respiratory distress (n = 3). Of the remaining 50 infants, complications developed in 34 (68%). These complications included strictures requiring further resection at the time of enterostomy closure in 20 infants; stricture of the enterostomy requiring surgical revision in 6; incisional hernia in 3; parastomal hernia in 4; enterostomal prolapse or intussusception in 6 and 1, respectively; wound dehiscence in 4; wound infection in 8; small-bowel obstruction requiring laparotomy in 2; and anastomotic complications in 2. Only 16 enterostomies were closed uneventfully, with 3 of these infants subsequently dying of sudden infant death syndrome between 6 and 8 months after the operation. Of the surviving infants, 3 (6%) continue to require home hyperalimentation. CONCLUSIONS: Although enterostomy in infants with low birth weight with necrotizing enterocolitis may be lifesaving, it is also a major cause of morbidity. These data suggest the feasibility of a prospective study comparing resection and primary anastomosis with resection and enterostomy.

Enterocolitis, Pseudomembranous↗

UV-DNA damage in mouse and human cells induces the expression of tumor necrosis factor alpha.

Ultraviolet light induces the expression of tumor necrosis factor alpha (TNF alpha) in many mammalian cells. We have examined the signal for this induction in a human DNA repair-deficient cell line carrying a transgene composed of the murine TNF regulatory sequences fused to the chloramphenicol acetyltransferase (CAT) structural gene. When compared by fluence, UVC was a more efficient inducer of CAT than was UVB, but they were equivalent inducers when compared by the frequency of cyclobutyl pyrimidine dimers produced by each source. Further, treatment of UV-irradiated cells with the prokaryotic DNA repair enzyme T4 endonuclease V increased the level of repair of dimers and concomitantly reduced CAT gene expression. Membrane-bound TNF alpha expression was increased by UV and reduced by repair of dimers. Finally, in the TNFcat transgene system, DNA damage directly to the cell with the transgene was required as cocultivation of unirradiated TNFcat cells with UV-irradiated cells did not increase CAT activity. These results show that DNA damage is a signal for the induction of TNF alpha gene expression in mouse and human cells.

Animals↗

The repeat organizer, a specialized insulator element within the intergenic spacer of the Xenopus rRNA genes.

We have identified a novel activity for the region of the intergenic spacer of the Xenopus laevis rRNA genes that contains the 35- and 100-bp repeats. We devised a new assay for this region by constructing DNA plasmids containing a tandem repeat of rRNA reporter genes that were separated by the 35- and 100-bp repeat region and a rRNA gene enhancer. When the 35- and 100-bp repeat region is present in its normal position and orientation at the 3' end of the rRNA reporter genes, the enhancer activates the adjacent downstream promoter but not the upstream rRNA promoter on the same plasmid. Because this element can restrict the range of an enhancer's activity in the context of tandem genes, we have named it the repeat organizer (RO). The ability to restrict enhancer action is a feature of insulator elements, but unlike previously described insulator elements the RO does not block enhancer action in a simple enhancer-blocking assay. Instead, the activity of the RO requires that it be in its normal position and orientation with respect to the other sequence elements of the rRNA genes. The enhancer-binding transcription factor xUBF also binds to the repetitive sequences of the RO in vitro, but these sequences do not activate transcription in vivo. We propose that the RO is a specialized insulator element that organizes the tandem array of rRNA genes into single-gene expression units by promoting activation of a promoter by its proximal enhancers.

Animals↗

Guilty but insane: the insanity defence in Ireland, 1850-1995.

BACKGROUND: This is a retrospective study describing sociodemographic and clinical characteristics of an almost complete sample of insanity acquittees in Ireland between 1850-1995. METHOD: Case records and legal files were examined for each of the 437 patients admitted to the Central Mental Hospital under guilty but insane criteria, and a profile of sociodemographic, forensic and clinical data completed in each. RESULTS: The number of insanity acquittees has fallen five-fold since the 19th century. Acquittees were usually single males from rural areas, aged in their 30s, who had committed a violent crime while suffering from a major psychiatric illness. Female insanity acquittees were relatively few in number and were equally likely to have been charged with violent crime, especially against their own children. The mean length of detention was 14.5 years. CONCLUSIONS: The insanity defence is rarely used in Ireland, is largely confined to serious offences (especially homicide), and generally results in prolonged detention.

Crime↗