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Biomedical subjects

S Haines

Publications and source records attributed to S Haines.

At least 19 recordsLinked to original sources

Fibrinolytic therapy for intraventricular hemorrhage in adults.

BACKGROUND: Spontaneous or secondary intraventricular hemorrhage is a marker of poor prognosis for hemorrhagic stroke. It can cause hydrocephalus and require ventricular shunt placement, result in permanent neurological deficits or death. Fibrinolytic agents injected into the ventricular system could dissolve blood clots, increase the clearance of blood from the ventricles and hence improve outcome. OBJECTIVES: To assess the clinical efficacy and safety of thrombolytic agents administered intraventricularly in the management of intraventricular hemorrhage in adults. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched February 2002). In addition, we searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Current Contents, and International Pharmacy Abstracts to 2001. We handsearched several neurosurgery journals and the references list of articles identified. SELECTION CRITERIA: Randomised unconfounded studies comparing intraventricular fibrinolytic therapy to placebo or open control for the management of intraventricular hemorrhage in adults. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed all identified trials. Clinically significant information related to patient population, efficacy and safety were extracted and summarized. MAIN RESULTS: A total of ten studies were identified by our search strategy. Eight of them were excluded because of case series designs or retrospective control group. One quasi-randomised trial used alternate allocation and was excluded. Only one report met the review criteria for randomization. The randomised trial reported good outcome but has important design flaws resulting in a biased control group and therefore was excluded. REVIEWER'S CONCLUSIONS: There is anecdotal evidence suggesting that the intraventricular administration of fibrinolytic agents in intraventricular hemorrhage maybe of therapeutic value and safe. Thus far, there are no randomised trials of sufficient size and quality to evaluate the safety and efficacy of this treatment modality.

Adult↗

Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome.

This open pilot study of vagus nerve stimulation (VNS) in 60 patients with treatment-resistant major depressive episodes (MDEs) aimed to: 1) define the response rate; 2) determine the profile of side effects; and, most importantly; 3) establish predictors of clinical outcome. Participants were outpatients with nonatypical, nonpsychotic, major depressive or bipolar disorder who had not responded to at least two medication trials from different antidepressant classes in the current MDE. While on stable medication regimens, the patients completed a baseline period followed by device implantation. A 2-week, single blind, recovery period (no stimulation) was followed by 10 weeks of VNS. Of 59 completers (one patient improved during the recovery period), the response rate was 30.5% for the primary HRSD(28) measure, 34.0% for the Montgomery-Asberg Depression Rating Scale (MADRAS), and 37.3% for the Clinical Global Impression-Improvement Score (CGI-I of 1 or 2). The most common side effect was voice alteration or hoarseness, 55.0% (33/60), which was generally mild and related to output current intensity. History of treatment resistance was predictive of VNS outcome. Patients who had never received ECT (lifetime) were 3.9 times more likely to respond. Of the 13 patients who had not responded to more than seven adequate antidepressant trials in the current MDE, none responded, compared to 39.1% of the remaining 46 patients (p =.0057). Thus, VNS appears to be most effective in patients with low to moderate, but not extreme, antidepressant resistance. Evidence concerning VNS' long-term therapeutic benefits and tolerability will be critical in determining its role in treatment-resistant depression.

Adolescent↗

Supporting ward staff in acute care areas: expanding the service.

Critical care services face significant change over the next five years; pressure on intensive care unit beds continues to escalate. As a result of service demands, there are still an increasing number of highly dependent patients being cared for in general ward areas, placing increasing pressures on the multi-professional team. There is now national recognition of these changing service requirements and wide-ranging proposals for improving the continuity and quality of care provided for critically ill patients within the NHS. The role of Clinical Nurse Educator Critical Care within one acute Trust over an 18-month period is reflected on and current expansion of the service in light of these national initiatives is explored.

Continuity of Patient Care↗

Providing continuity of care for patients transferred from ICU.

Patients requiring treatments previously only undertaken in critical care units are now being nursed in other ward areas. A study was carried out to determine the difficulties that are faced by ward nurses caring for this highly dependent patient group. Staff and patient stress were problems experienced and there was a call for closer liaison between ICU and ward staff.

Burnout, Professional↗

Vagus nerve stimulation (VNS) for treatment-resistant depressions: a multicenter study.

BACKGROUND: Vagus Nerve Stimulation (VNS) delivered by the NeuroCybernetic Prosthesis (NCP) System was examined for its potential antidepressant effects. METHODS: Adult outpatients (n = 30) with nonpsychotic, treatment-resistant major depressive (n = 21) or bipolar I (n = 4) or II (n = 5; depressed phase) disorders who had failed at least two robust medication trials in the current major depressive episode (MDE) while on stable medication regimens completed a baseline period followed by NCP System implantation. A 2-week, single-blind recovery period (no stimulation) was followed by 10 weeks of VNS. RESULTS: In the current MDE (median length = 4.7 years), patients had not adequately responded to two (n = 9), three (n = 2), four (n = 6), or five or more (n = 13) robust antidepressant medication trials or electroconvulsive therapy (n = 17). Baseline 28-item Hamilton Depression Rating Scale (HDRS(28)) scores averaged 38.0. Response rates (> or =50% reduction in baseline scores) were 40% for both the HDRS(28) and the Clinical Global Impressions-Improvement index (score of 1 or 2) and 50% for the Montgomery-Asberg Depression Rating Scale. Symptomatic responses (accompanied by substantial functional improvement) have been largely sustained during long-term follow-up to date. CONCLUSIONS: These open trial results suggest that VNS has antidepressant effects in treatment-resistant depressions.

Adolescent↗

Identification of transposon-tagged genes by the random sequencing of Mutator-tagged DNA fragments from Zea mays.

We have used a universal adaptor amplification procedure to isolate random Mutator-tagged fragments from Mutator-active maize plants. Direct sequence characterization of 761 Mutator-tagged fragments indicated that a significant number were homologous to sequences within the public databases. The ability of Mutator-tagged fragments to detect homology was not related to the length of the sequence within the range 100-400 bp. However, fragments above this size did show an increased chance of detecting homology to either expressed sequence tags or genes. Characterization of the insertion sites of the Mutator elements suggested that while it does target transcribed regions, Mutator does not appear to have any site preference within the transcription unit. Hybridization of previously unidentified Mutator-tagged fragments to arrayed cDNA libraries confirmed that many of these also showed homology to transcribed regions of the genome. Examination of back-crossed progeny confirmed that all the insertions examined were germinal; however, in all but one case, selfing five individual Mutator-tagged lines failed to reveal an obvious phenotype. This study suggests that the random sequencing of Mutator-tagged fragments is capable of producing both a significant number of interesting transposon tagged genes and mutant plant lines, all of which could be extremely valuable in future gene discovery and functional genomics programmes.

Amino Acid Sequence↗

Long-term follow-up data from the Shunt Design Trial.

BACKGROUND: A previously reported multicenter randomized trial assessed whether 2 new shunt valve designs would reduce shunt failure rates compared to differential pressure valves. The study did not show a significant difference in the time to first shunt failure. Patients entered the trial between October 1, 1993, and October 31, 1995. The primary results were based on the patients' status as of October 31, 1996 (a minimum follow-up of 1 year). This report describes the late complications based on the patients' most recent follow-up. METHODS: Three hundred and forty-four hydrocephalic children at 12 North American and European centers were randomized to 1 of 3 valves: a standard differential pressure valve; a Delta valve (PS Medical-Medtronic) or a Sigma valve (NMT Cordis). Patients were followed until their first shunt failure. Shunt failure was defined as shunt surgery for obstruction, overdrainage, loculation or infection. If the shunt did not fail, follow-up was continued until August 31, 1999. RESULTS: One hundred and seventy-seven patients had shunt failure. Shunt obstruction occurred in 131, overdrainage in 13, loculated ventricles in 2 and infection in 29. The overall shunt survival was 62% at 1 year, 52% at 2 years, 46% at 3 years, 41% at 4 years. The survival curves for the 3 valves were similar to those from the original trial and did not show a survival advantage for any particular valve. CONCLUSIONS: Prolonged follow-up to date does not alter the primary conclusions of the trial: there does not appear to be one valve that is clearly the best for the initial treatment of pediatric hydrocephalus.

Adolescent↗

Randomized trial of cerebrospinal fluid shunt valve design in pediatric hydrocephalus.

OBJECTIVE: Forty percent of standard cerebrospinal fluid shunts implanted for the treatment of pediatric hydrocephalus fail within the first year. Two new shunt valves designed to limit excess flow, particularly in upright positions, were studied to compare treatment failure rates with those for standard differential-pressure valves. METHODS: Three hundred-forty-four hydrocephalic children (age, birth to 18 yr) undergoing their first cerebrospinal fluid shunt insertion were randomized at 12 North American or European pediatric neurosurgical centers. Patients received one of three valves, i.e., a standard differential-pressure valve; a Delta valve (Medtronic PS Medical, Goleta, CA), which contains a siphon-control component designed to reduce siphoning in upright positions; or an Orbis-Sigma valve (Cordis, Miami, FL), with a variable-resistance, flow-limiting component. Patients were monitored for a minimum of 1 year. Endpoints were defined as shunt failure resulting from shunt obstruction, overdrainage, loculations of the cerebral ventricles, or infection. Outcome events were assessed by blinded independent case review. RESULTS: One hundred-fifty patients reached an endpoint; shunt obstruction occurred in 108 (31.4%), overdrainage in 12 (3.5%), loculated ventricles in 2 (0.6%), and infection in 28 (8.1%). Sixty-one percent were shunt failure-free at 1 year and 47% at 2 years, with a median shunt failure-free duration of 656 days. There was no difference in shunt failure-free duration among the three valves (P = 0.24). CONCLUSION: Cerebrospinal fluid shunt failure, predominantly from shunt obstruction and infection, remains a persistent problem in pediatric hydrocephalus. Two new valve designs did not significantly affect shunt failure rates.

Adolescent↗

Spreading and retention of vaginal formulations in post-menopausal women as assessed by gamma scintigraphy.

PURPOSE: In this paper we report on the first scintigraphic evaluation of vaginal dosage forms in post-menopausal women. To date, almost nothing is known about the in vivo performance of pharmaceutical formulations in the human vagina, which is a major deficiency in the rational design of drug delivery systems for both existing and new indications. METHODS: The vaginal spreading and clearance of a radiolabelled pessary formulation and Replens (polycarbophil) gel, was assessed in six healthy, post-menopausal female volunteers over a six hour period using the technique of gamma scintigraphy. RESULTS: In five out of the six subjects studied, clearance of the two formulations exhibited very little intra-subject variation. However, there was considerable inter-subject variability in clearance; in Subject 5 circa 80% of the products were retained whilst in Subject 2 less than 2% was present at the end of the six hour imaging period. Importantly, there was no evidence to suggest that either of the formulations dispersed material beyond the cervix, into the uterus, in any of the subjects studied. CONCLUSIONS: The lack of significant retention of these products in most of the volunteers has obvious implications for the delivery of therapeutic agents. This study shows that gamma scintigraphy is an invaluable technique with which to assess novel formulations aimed at optimising retention in the vagina for topical or systemic drug delivery.

Administration, Intravaginal↗

Colonic spread of three rectally administered mesalazine (Pentasa) dosage forms in healthy volunteers as assessed by gamma scintigraphy.

BACKGROUND: Rectal administration of enemas, foams and suppositories is the most efficient method of delivering locally-acting drugs to the distal colon, sigmoid colon and rectum. Healthy volunteers provide an effective population to compare different formulations for rectal drug delivery. However, there is still only limited comparative information available on the dispersion of such dosage forms in human subjects. Therefore, the objective of this scintigraphic study was to compare colonic spread of an enema, a rectal foam and a suppository formulation in healthy volunteers. METHODS: This was a randomized, crossover study in eight healthy male volunteers. Each received Pentasa rectal formulations as either a 100 mL suspension enema (1 g mesalazine), one actuation of a non-CFC propellant rectal foam (1 g mesalazine in 5 mL concentrate, expanding to 40 mL on actuation), or one suppository (1 g mesalazine) on three separate occasions. The spread of the radiolabelled formulations was assessed over a 4-h period by gamma scintigraphy. RESULTS: The formulations were retained by all subjects for the whole of the 4-h imaging period. The enema spread to the splenic flexure in 7 out of 8 subjects, but was retained in the rectum and sigmoid colon in one individual. The foam spread as far as the descending colon in four subjects. In the remaining individuals the foam was retained in the rectum and sigmoid colon. The spread of the suppository was limited and confined to the rectum. CONCLUSIONS: The findings of this study are consistent with previous research and support the intended clinical uses of the enema, foam and suppository formulations to treat distal ulcerative colitis, proctosigmoiditis and proctitis, respectively. The results highlight the potential of gamma scintigraphy in providing in vivo 'proof of concept' data to help verify the targeting of pharmaceutical products to their intended site of delivery.

Administration, Rectal↗

Evaluating hearing threshold differences between ears as a screen for acoustic neuroma.

Differences in pure tone thresholds between ears were evaluated at two different patient care facilities to determine this measure's value as a screen for acoustic neuroma. We evaluated the audiograms of tumor and nontumor groups to estimate the true positive rates and false positive rates for several decision rules. Threshold differences were found to be a more effective diagnostic tool for females than for males. However, even for the most effective rules, the efficiency of this test alone is mediocre, which indicates that hearing threshold differences between ears must be combined with other criteria for a cost-effective approach to acoustic neuroma identification. Furthermore, tumor size was not predicted by the amount of threshold asymmetry between ears, which suggests that some large, potentially life-threatening tumors may be missed if pure tone threshold differences are the sole criterion for referral for additional tests.

Adult↗

Prototype instruments for endoscopic microsurgery: technical note.

The authors describe a concept of converting microsurgical instruments into endoscopes and demonstrate prototype devices. These instruments combine the benefits of microsurgery (multiple instruments, tactile feedback, bimanual manipulation, magnification) with those of endoscopy (minimally invasiveness, indirect line of vision).

Animals↗

VASE exon expression alters NCAM-mediated cell-cell interactions.

The neural cell adhesion molecule (NCAM) is found on cells as several related polypeptides formed by alternative splicing of the single NCAM gene. The alternatively spliced 30-bp VASE exon in the fourth immunoglobulin-like domain is the structural variation nearest those portions of the polypeptide proposed to mediate cell-cell adhesion. To test the ability of distinct forms of the NCAM molecules to mediate cell adhesion, L cells were transfected with expression vectors encoding rat 140 kD NCAM +/- the VASE exon. L cell lines which expressed these polypeptides were isolated and tested for self-aggregation in a low shear, rapid aggregation assay. Increased cellular aggregation of the transfectants was observed to be a function of the NCAM molecule expressed. These transfected cells showed segregation in a long term co-aggregation assay: cells expressing NCAM--VASE formed aggregates which tended to exclude cells expressing NCAM+VASE and vice versa. These results provide direct evidence that this small difference in NCAM structure is sufficient to allow segregation of cells.

Animals↗

Axon growth is enhanced by NCAM lacking the VASE exon when expressed in either the growth substrate or the growing axon.

The neural cell adhesion molecule NCAM exists as several related peptides formed by alternative splicing of the single NCAM gene. Here the ability of NCAM containing and lacking the alternatively spliced VASE exon to act as a permissive growth substrate was tested by examining retinal axon outgrowth on normal L cell fibroblasts and L cells expressing stably transfected 140 kD NCAM +/- VASE. L cells expressing either NCAM form were a more permissive substrate than control L cells. At higher substrate cell densities, greater axon outgrowth occurred on substrate cells expressing NCAM - VASE than on those expressing NCAM + VASE. Similar experiments tested retinal axon growth on neuronal substrates by utilizing clonal B35 cells, C3 cells that are NCAM lacking variants of B35, and C3 cells into which 140 kD NCAM +/- VASE has been restored by transfection. Axon growth on C3 cells transfected with NCAM - VASE was greater than that on all other substrates including cells transfected with NCAM + VASE. In these experiments C3 cells and transfected C3 expressing NCAM + VASE cell promoted similar outgrowth. The influence on neurite growth of the NCAM isoform of the neurite itself was tested by examining neurite formation using combinations of C3 cells and C3 NCAM transfectants both in the growth monolayer and as responding cells. C3 cells were able to extend neurites, indicating NCAM is not required for neurite growth. However, C3 derivatives transfected with NCAM +/- VASE had greater neurite outgrowth. The most extensive neurite growth was found when NCAM - VASE was expressed by both substrate cells and the responding neurite growing cells. Thus NCAM enhances axon or neurite outgrowth when present either in the growth substrate or on the growing axon. NCAM - VASE has a significantly greater growth promoting capability than NCAM + VASE. The expression of NCAM + VASE by more mature neural cells could thus be a significant factor in the reduced axonation capabilities of mature neurons.

Animals↗

Clinical management of a hemodialysis patient with metastatic hypernephroma receiving experimental alfa interferon therapy.

The nursing interventions needed to promote optimal care for D.S. forcefully reminded the nurses of the challenges of nursing practice. The physiologic and emotional impact of the disease processes (ESRD and cancer), and the nature of chronic illness with concurrent experimental interferon therapy required continuous attention as the combined therapies progressed. The goals and interventions outlined are familiar to nephrology nurses. They are very effective in assisting this patient to adjust and to meet the expected outcomes. The unique nature of every patient remains the constant in our clinical practice. Nursing must continue to forge ahead in assessing a patient's needs, but always remembering that these needs must support the patient's relationship with his/her world.

Carcinoma, Renal Cell↗