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Biomedical subjects

S Donnelly

Publications and source records attributed to S Donnelly.

At least 37 records · Page 2Linked to original sources
PubMed1999

Glycerol-induced seizure: involvement of IL-1beta and glutamate.

It is widely accepted that interleukin-1beta (IL-1beta), a cytokine produced not only by cells of the immune system but also by cells of the central nervous system, modulates hippocampal function. Here we investigate the effect of a seizure-induced increase in hippocampal IL-1beta concentration on neurotransmitter release. We report that oral administration of glycerol evoked seizure activity in BALB/c mice. Associated with these convulsions was an induction of IL-1beta gene expression and a significant increase in cytokine protein in the hippocampus. Release of glutamate in synaptosomes prepared from hippocampi of these animals was reduced compared to control. These results are consistent with previous data suggesting a modulatory effect of IL-1beta on glutamate release in hippocampus.

Animals↗
PubMed1999

Erythropoietin deficiency in hyporeninemia.

The association of anemia and hyporeninemic hypoaldosteronism (HRHA) in type 1 diabetes has been described, and erythropoietin deficiency has been proposed as the cause. Subjects with type 1 diabetes with (n = 8) and without HRHA (n = 11) were studied, as were subjects taking angiotensin-converting enzyme inhibitors (ACEIs; n = 10). Renal function and sodium excretion were estimated with a 24-hour urine collection. Values for hemoglobin, hematocrit, serum erythropoietin, and red blood cell volume were determined. HRHA subjects were anemic (hemoglobin, 99 +/- 8 g/L ), and ACEI subjects had lower hemoglobin concentrations (120 +/- 4 g/L) compared with controls (134 +/- 3 g/L; P < 0.001 and P = 0.01, respectively). Also, the red cell mass in patients with HRHA was significantly less than that in controls (14.8 +/- 1.4 v 20.8 +/- 1.1 mL/kg; P = 0.004), indicating that the lower hemoglobin level in HRHA is not attributable to an expansion of extracellular volume. Erythropoietin levels in the HRHA (27% +/- 11% of predicted) and ACEI groups (43% +/- 9% of predicted) were low compared with controls (94% +/- 13% of predicted; P = 0.001 and P = 0.005, respectively). Renal function was greater than the levels at which anemia becomes a clinical feature in all groups, but creatinine clearance was less in the HRHA (63 +/- 12 mL/min/1.73 m2) and ACEI groups (76 +/- 11 mL/min/1.73 m2) compared with controls (123 +/- 9 mL/min/1.73 m2; P < 0.001 and P = 0.004, respectively). The fractional sodium reabsorption was decreased in HRHA (98.7% +/- 0.3%) and ACEI groups (98.7% +/- 0.3%) versus controls (99.4% +/- 0.1%; P = 0.007 and P = 0.01, respectively). Subjects with type 1 diabetes with HRHA had low hemoglobin concentrations that were caused, at least in part, by inappropriately low serum erythropoietin levels.

Adult↗
PubMed1999

Axonal cytoskeletal responses to nondisruptive axonal injury and the short-term effects of posttraumatic hypothermia.

In human diffuse axonal injury (DAI), axons are exposed to transient tensile strain. Over the ensuing several hours, injured axons enter a "pathological cascade" of events that lead to secondary axotomy. Use of animal models of traumatic axonal injury (TAI) has allowed description of a number of pathological changes before axotomy occurs, including structural and functional changes in the axolemma, disorientation, and/or loss of microtubules, either compaction and/or dispersion of neurofilaments together with focal compaction at sites where continuity of the axolemma is lost. Recent literature suggests that use of hypothermia may improve behavioral outcomes or reduce the number/density of injured axons in which axonal transport is altered after TAI. But there is presently no ultrastructural, pathological explanation as to how hypothermia may act at the level of the axon to reduce posttraumatic loss of axoplasmic transport. In this study, we tested the hypothesis that posttraumatic hypothermia may ameliorate (a) alteration of axonal transport and (b) early pathological changes in the axonal cytoskeleton prior to secondary axotomy. We have undertaken a pilot study within 4 h of stretch injury to adult guinea pig optic nerve axons as a model of TAI and applied stereological techniques to assess differences in pathology in animals either maintained at 37.5 degrees C or cooled to 32-32.5 degrees C for 2 or 4 h after injury. We provide quantitative evidence that posttraumatic hypothermia significantly reduces the number of axons labelled for beta-APP, a marker for disruption of fast axonal transport, and reduces the loss of microtubules and compaction of neurofilaments, which occurs in normothermic animals over the first 4 h after injury.

Amyloid beta-Protein Precursor↗
PubMed1999

Hyaluronic acid in the treatment of osteoarthritis of the knee.

OBJECTIVES: We examined the efficacy, safety and patient satisfaction of intra-articular hyaluronic acid (HA) in patients with osteoarthritis of the knee. METHODS: One hundred patients with mild to moderate osteoarthritis of the knee entered a randomized blind-observer trial of 6 months HA vs placebo. Primary efficacy criteria were pain on walking, measured with a visual analogue scale, and the Lequesne Index. RESULTS: For pain on walking, a significant difference in favour of HA was found for completed patients at week 5, the end of the course of injections, and at month 6, the end of the study (P = 0.0087 and P = 0.0049, respectively). Further analysis using the Last Observation Carried Forward (LOCF) also showed a significant benefit favouring HA at month 6 (P = 0.0010). For the Lequesne Index, a significant difference in favour of HA was found at week 5 (P = 0.030) and at month 2 (P = 0.0431), but this was only of borderline significance at month 4 (P = 0.0528). Patients' global assessment of efficacy favoured HA at month 6 (P = 0.012). Improvement in other secondary criteria was generally superior in the HA group compared to placebo both at week 5 and month 6. Adverse events, mainly local injection site reactions, occurred in both groups with equal frequency. CONCLUSIONS: The study demonstrated that five weekly intra-articular injections of sodium hyaluronate (Hyalgan) were superior to placebo and well tolerated in patients with osteoarthritis of the knee with a symptomatic benefit which persisted for 6 months.

Adjuvants, Immunologic↗
PubMed1999

Folklore associated with dying in the west of Ireland.

The warm welcome for modern advances in the care of the dying should not exclude the past in which there is much to be learned from the skills of our ancestors. A bilingual two-year qualitative research project into traditions associated with dying and death was undertaken. Research began in the archives available in the internationally recognized university folklore departments of Ireland and Scotland. This was augmented by 40 indepth personal interviews with Gaelic- and English-speaking residents in rural communities of both countries, recalling local customs and practices in the care of the dying. This paper reports the Irish experience; the collection of data in Scotland continues. From this study, several main themes emerged. Death was seen and accepted as a natural continuation of life, simply a step into the spirit world. In view of people's oneness with nature and the spiritual world, death was not to be feared. Traditions were unique to each area even down to the precise number of candles used at the sickbed. People understood the signs and symptoms of dying and were skilled in alleviating the distress of both relatives and the dying; and, in this, language was important in capturing and expressing the philosophy of these people. The acceptance of death as the one truism of life was facilitated by the strong faith and prayer of people for whom, in the celebration of death, humour was never far away. In their grief, the community was supported by the loose formality of the wake (torramh), funeral procession, keening (caoineadh) and music. In all these, the men and women of the community and its leaders had distinct and respected roles to play.

Attitude to Death↗
PubMed1998

Long-term clinical outcome following coronary artery bypass grafting for isolated stenosis of the left anterior descending coronary artery.

AIMS: To detail the clinical and angiographic profile, and long-term outcome in consecutive patients with isolated stenosis of the left anterior descending coronary artery undergoing bypass surgery. METHODS: A retrospective study of all patients (n = 301) (January 1984-December 1990) and undergoing coronary artery bypass grafting for isolated left anterior descending disease, in the Irish Republic, was performed. Survival was compared with that of an exact age- and gender-matched cohort. RESULTS: Mean age was 53 (+/- 9.3) years. There were 238 (79%) males. In 241 (80%) patients an internal thoracic arterial bypass graft was used. Operative mortality was 1.3%. Of the 280 (93%) patients alive (16 cardiac deaths) at 7.1 (+/- 1.9) years, 105 (35%) had angina, 26 (9%) suffered an interval myocardial infarction, and repeat revascularization was required on 29 (10%). Female gender (P = 0.002), pre-operative myocardial infarction (P = 0.02), significant diagonal disease (P = 0.04) and postoperative myocardial infarction (P = 0.0001) were independently associated with survival. Females were more likely to develop congestive cardiac failure (P = 0.01) or postoperative angina (P = 0.03) than their male counterparts. CONCLUSIONS: Survivorship (97%) and event-free survival (96%) at 5 years following coronary artery bypass grafting for isolated left anterior descending coronary artery disease is excellent and equivalent to an age-matched and gender-matched cohort.

Adult↗
PubMed1998

Effects of cyclical etidronate combined with calcitriol versus cyclical etidronate alone on spine and femoral neck bone mineral density in postmenopausal osteoporotic women.

OBJECTIVES: Few data are available on the effects of combination therapy for the treatment of osteoporosis. The aim of this study was to compare the effects of intermittent cyclical etidronate (E) therapy alone with a combination of cyclical etidronate and calcitriol (E + C) on spine and femoral neck bone mineral density (BMD) at one year. METHODS: Postmenopausal women with at least one non-traumatic vertebral fracture or z score < -1.5 were randomly allocated to an E group (each cycle = oral etidronate 400 mg daily for 14 days followed by calcium 500 mg daily for 76 days) or an E + C group (as for E plus oral calcitriol 0.5 microgram daily). Lumbar spine and femoral neck BMDs were measured by dual energy x ray absorptiometry at baseline and at one year. The study design did not contain a placebo group. RESULTS: The mean % increase in lumbar spine BMD was 5.2% (95% CI = 3.4 to 7.0) in the E + C group (n = 24), which was significantly greater than the 2.7% (95% CI = 1.3 to 4.1) increase in the E group (n = 23) (p < 0.05). The femoral neck BMD in the E + C group increased by 2.0% (95% CI = 0.8 to 3.2), which was significantly different from the E group where there was a -0.4% (95% CI = -2.4 to 1.6) change (p = 0.046). CONCLUSIONS: These data show that a combination of cyclical etidronate and calcitriol is better than cyclical etidronate alone in terms of changes in BMD at both spine and femoral neck sites. Although further data are needed on fracture efficacy, this study suggests that combination therapies have additive therapeutic potential that may exceed that expected from their theoretical mode of action.

Absorptiometry, Photon↗
PubMed1998

Patient management strategies for interferon alfa-2b as adjuvant therapy of high-risk melanoma.

PURPOSE/OBJECTIVES: To review results of Eastern Cooperative Oncology Group (ECOG) trial E1684 in the context of nursing issues concerning interferon alfa-2b (IFN alpha-2b) as adjuvant therapy for high-risk melanoma. DATA SOURCES: Published results of ECOG trial E1684 and additional safety data provided by the trial sponsor. Selection of material was based on information that would expand on published safety results and present patient-management strategies relevant to oncology nurses. DATA SYNTHESIS: High-dose IFN alpha-2b significantly prolonged median relapse-free survival (< 0.01) and overall survival (p = 0.047), but side effects required extensive nursing interventions. With appropriate patient management, including dose modifications, 74% of patients who did not relapse received a full course of therapy. CONCLUSIONS: Adjuvant, high-dose IFN alpha-2b can significantly prolong relapse-free and overall survival in patients with high-risk melanoma, but nursing interventions are required to ensure patient compliance. IMPLICATIONS FOR NURSING PRACTICE: Accurate nursing assessment and appropriate interventions can help patients safely complete this effective adjuvant therapy.

Antineoplastic Agents↗
PubMed1997

Phase IB trial of picibanil (OK-432) as an immunomodulator in patients with resected high-risk melanoma.

The microbial immunostimulant OK-432 has been studied intensively in preclinical systems and has shown promise as an anticancer agent in trials that have been conducted over the past 20 years in Japan. To date, no systematic dose response evaluation of this agent has defined its dose-limiting toxicity or immunobiological activity. A phase IA study has been conducted in 25 patients with metastatic cancer at the University of Pittsburgh Cancer Institute Melanoma Center, establishing 30 KE as the maximal tolerable dosage, on the basis of cutaneous reactions. Subsequently, 48 patients with resected high-risk melanoma participated in a phase IB study of OK-432. This study has evaluated the immunomodulatory activity of OK-432 at five dosages ranging from 1 KE to 20 KE, administered ID twice weekly for 3 months. A formal analysis of the treated population in comparison to the randomized control group has been conducted, and profound immunological effects have been defined in the group of patients treated with OK-432. Patients who participated in this trial had a significant depression of OK-432-inducible cytokine production (interleukin-1 beta, interferon gamma, and tumor necrosis factor alpha) at baseline. Treatment with OK-432 reversed this deficit for interferon gamma (IFN gamma) production in a dose-dependent manner, and mitigated the inhibition for interleukin-1 (IL-1) across all dosage groups. The impact of OK-432 upon other immunological functions of the treated cohorts is more variable, with durable suppression of mononuclear cell superoxide production, and in vitro cytotoxicity to tumor. Immunological characteristics of the entire cohort demonstrate a strong and significant correlation of elevated blood CD16+ cell counts and natural killer activity with early tumor progression and death due to melanoma. Favorable prognosis is associated with monocyte capacity to produce tumor necrosis factor (TNF), and polymorphonuclear leukocyte formylmethionyl-leucylphenylalanine-inducible superoxide release. This study reveals several new immunological correlates of tumor progression and lethal outcome in resected high-risk melanoma. It demonstrates that the depressed IL-1, TNF, and IFN gamma release associated with melanoma may be mitigated by treatment with OK-432. This study has defined treatment and dose response patterns of immunomodulation associated with one of the most complex immunological agents yet evaluated in phase IB trials, in a well-defined population of high-risk patients with resected melanoma.

Adjuvants, Immunologic↗
PubMed1996

Spiking of the tibial tubercles--a radiological feature of osteoarthritis?

OBJECTIVE: To determine whether 'spiking' or angulation of the tibial tubercle is associated with other radiographic markers of osteoarthritis (OA) or pain in the knee joint, and could be taken as a reliable marker for early OA, in a large general population sample. METHODS: A total of 950 women from the Chingford general population survey underwent anteroposterior extended weight bearing radiography of the knees. Angulation of the tip of the medial and lateral tubercles, and height of the tubercles above the tibial plateau were measured. These measures were compared with standard radiographic indices including qualitative Kellgren and Lawrence global score, individual scores of osteophytes and joint space narrowing, and pain score. Intraobserver and interobserver reproducibility for assessment of spiking was tested in a subgroup of 50 films using two observers and two readings. Tibial spiking (angulation and height) was defined for this study as the top 10th centile for the whole population. Patients with normal radiographs (Kellgren and Lawrence grade 0) were allocated to quartile groups on the basis of spiking to define severity. Odds ratios were then calculated for the association of spiking and knee pain. RESULTS: The majority of the measures of tibial spiking were highly reproducible. There was a significant correlation between tibial spike angulation and the presence of osteophytes, but not joint space narrowing. The correlations for spike height with osteophytes and joint space narrowing were poor. There was an association between spike angulation at the lateral tubercle and reported knee pain (odds ratio 1.45 (95% confidence interval 1.03 to 2.03)) after adjustment for age, body mass index, and Kellgren and Lawrence score. There was no association between medial spike angulation or spike height and pain. Among the 950 women, 683 (72%) had normal radiographs (Kellgren and Lawrence = 0); in this group there was a similar association between pain and lateral spike angulation, but not medial spike angulation or spike height. CONCLUSIONS: Tibial spiking is associated with the presence of knee osteophytes and is reproducible, but does not have a strong independent relationship with knee pain. In patients with normal radiographs there is no useful correlation between tibial spiking and pain. Isolated tibial spiking is not a reliable sign of early knee OA, and should not routinely be reported.

Aged↗
PubMed1996

Quality of life assessment in advanced cancer.

Our purpose is to examine how applicable current quality of life instruments are in advanced cancer. Quality of life (QOL) is difficult to define and measure; it is a multidimensional, dynamic and subjective concept. An acceptable QOL instrument for advanced disease should be simple to administer and easy to explain, complete and analyse. In our view, the present instruments used in oncology do not serve the needs of advanced cancer patients. Based on our review, we believe a single question posed on a linear or categorical scale should be used to assess QOL in advanced cancer in preference to other available methods.

Humans↗
PubMed1996

Carmustine and streptozocin in refractory melanoma: an attempt at modulation of O-alkylguanine-DNA-alkyltransferase.

The activity of the enzyme O6-alkylguanine-DNA-alkytransferase (AGAT) protects cells from the cytotoxic effects of alkylating agents. This Phase II trial was designed to assess the efficacy of a strategy designed to modulate the resistance to carmustine (BCNU) mediated by AGAT using streptozocin (STZ) in patients with advanced refractory melanoma. Seventeen patients who had failed prior chemotherapy were treated with STZ at 500 mg/m2 daily for 4 days with BCNU at 150 mg/m2 on day 3. Peripheral blood lymphocytes for assay of AGAT activity levels were collected prior to therapy and following the third dose of STZ. There were two partial responses in the 15 patients evaluable for response (13%). Most patients received only a single cycle of therapy due to rapidly progressive disease. Two patients developed fatal pulmonary toxicity, and one developed myelodysplasia. Other toxicities included transient rises in liver function tests. AGAT levels decreased by a mean of 53% in 9 patients but actually increased over baseline in 3 patients while on therapy. Based on these data, BCNU and STZ are not an effective combination for the therapy of advanced refractory melanoma, and pulmonary toxicity due to this combination appears to be increased compared with BCNU alone. STZ is not an effective modulator of AGAT activity when given on this schedule. New strategies designed to deplete AGAT activity using O6-benzylguanine or temozolomide should be explored with careful attention to the possibility that this approach may potentiate both the toxicity and efficacy of BCNU.

Adult↗
PubMed1995

Familial Hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3.

We have mapped a disease locus for Wolff-Parkinson-White syndrome (WPW) and familial hypertrophic cardiomyopathy (FHC) segregating in a large kindred to chromosome 7 band q3. Although WPW syndrome and FHC have been observed in members of the same family in prior studies, the relationship between these two diseases has remained enigmatic. A large family with 25 surviving individuals who are affected by one or both of these conditions was studied. The disease locus is closely linked to loci D7S688, D7S505, and D7S483 (maximum two point LOD score at D7S505 was 7.80 at theta = 0). While four different FHC loci have been described this is the first locus that can be mutated to cause both WPW and/or FHC.

Adolescent↗
PubMed1995

The symptoms of advanced cancer.

The incidence and mortality of cancer are increasing. In advanced cancer when cure is impossible, symptoms should be the focus of attention. We review our recent prospective studies on symptom prevalence and severity in 1,000 patients with advanced cancer. Advanced cancer patients are polysymptomatic. Symptom prevalence differs with age, gender, and cancer site. The pattern of gastrointestinal symptoms is related to gender and severe weight loss. Specific symptoms are associated with reduced survival. There is a gender difference in survival favoring females. Pain, easy fatigue, and anorexia are consistently among the 10 most prevalent symptoms at all 17 primary sites. When pain, anorexia, weakness, anxiety, lack of energy, easy fatigue, early satiety, constipation, and dyspnea were present, 60% to 80% of patients rated them as moderate or severe, ie, of clinical importance. The most common symptoms also are the most severe. In general, the same symptoms are clinically important at most primary sites.

Adolescent↗
PubMed1995

The symptoms of advanced cancer: identification of clinical and research priorities by assessment of prevalence and severity.

In advanced cancer, when cure is impossible, symptoms should be the focus of attention. We report the first prospective, systematic analysis of the severity of 37 symptoms in 1000 patients with advanced cancer, using the Paradox relational database. Pain, easy fatigue, and anorexia were consistently among the 10 most prevalent symptoms associated with cancer at all sites. When pain, anorexia, weakness, anxiety, lack of energy, easy fatigue, early satiety, constipation, and dyspnea were present 60%-80% of patients rated them as moderate or severe, i.e. of clinical importance. The most common symptoms were also the most severe. In general the same symptoms were clinically important at most primary sites. Clinically important dyspnea, hoarseness, hiccough, and dysphagia were more common in men; anxiety, nausea, vomiting, and early satiety in women. Clinically important dyspepsia, nausea, and vomiting occurred more frequently in gynecological cancers.

Aged↗
PubMed1994

Bone mineral density and vertebral compression fracture rates in ankylosing spondylitis.

OBJECTIVE: To examine the relationship between disease severity and bone density as well as vertebral fracture risk in patients with ankylosing spondylitis (AS). METHODS: Measurements were taken for bone mineral density (BMD) and vertebral fracture rates in 87 patients with AS. BMD was measured at the hip (femoral neck -FN), lumbar spine (L1-L4-LS) and for the whole body using a hologic-QDR-1000/W absorptiometer. An algorithm based on normal female ranges of vertebral heights was used to define a fracture as occurring when two vertebral ratios were each three standard deviations below the calculated mean of the controls. RESULTS: Patients with AS had significantly lower FN-BMD in proportion to disease severity (based on a Schober index) and disease duration. LS-BMD was also reduced in early disease, but in patients with advanced AS it had increased considerably. Nine vertebral fractures (10.3%) were identified which was considerably higher than expected when compared with a fracture of 1.9% in a control population of 1035 females of a similar age range. Patients with AS with fractures were significantly older, more likely to be male, had longer disease duration and more advanced spinal limitation with less mobility. There was no significant reduction in lumbar spine or femoral neck bone density in the fracture group. CONCLUSIONS: Vertebral fractures that result from osteoporosis are a feature of longstanding AS. BMD used as a measure of osteoporosis of the spine in advanced AS is unreliable probably as a result of syndesmophyte formation and does not predict the risk of vertebral fracture. Alternative sites such as the neck of the femur should be used for sequential assessment of BMD in AS.

Adult↗