Single-nucleotide polymorphisms in the public domain: how useful are they?

There is a concerted effort by a number of public and private groups to identify a large set of human single-nucleotide polymorphisms (SNPs). As of March 2001, 2.84 million SNPs have been deposited in the public database, dbSNP, at the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/SNP/). The 2.84 million SNPs can be grouped into 1.65 million non-redundant SNPs. As part of the International SNP Map Working Group, we recently published a high-density SNP map of the human genome consisting of 1.42 million SNPs (ref. 3). In addition, numerous SNPs are maintained in proprietary databases. Our survey of more than 1,200 SNPs indicates that more than 80% of TSC and Washington University candidate SNPs are polymorphic and that approximately 50% of the candidate SNPs from these two sources are common SNPs (with minor allele frequency of > or =20%) in any given population.

Patients with cancer holding their own records: a randomised controlled trial.

BACKGROUND: The burden of cancer care in general practice is increasing. Patient-held records may facilitate effective, coordinated care, but no randomised controlled trials of their use in cancer care have been conducted, and concerns about possible negative effects remain. AIM: To evaluate the use of a supplementary patient-held record in cancer care. METHOD: Six hundred and fifty radiotherapy outpatients with any form of cancer were randomised either to hold a supplementary record or to receive normal care. It was explained to record holders that the supplementary record was intended to improve communication with health professionals and act as an aide memoire. After three months, patients' satisfaction with communication and with participation in their own care were assessed. Global health status, emotional functioning, and cognitive functioning were measured using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire. RESULTS: There were no significant differences between groups in any of the outcome measures. Patients in both groups expressed a high level of satisfaction with communication and participation in their care. Mean (SD) scores in the intervention and control groups were: global health status, 66.8 (24.2) and 65.3 (23.7); emotional functioning, 75.0 (24.6) and 77.4 (22.8); cognitive functioning, 84.5 (21.0) and 84.0 (21.3). CONCLUSION: A supplementary patient-held record for radiotherapy outpatients appears to have no effect on satisfaction with communication, participation in care, or quality of life.

Nephrosplenic entrapment in the horse: a retrospective study of 174 cases.

The clinical findings and outcome of 161 horses diagnosed with 174 episodes of nephrosplenic entrapment (NSE) were reviewed retrospectively. The median age at presentation was 5 years (9 months to 24 years), and duration of colic was 2-92 h. Nasogastric reflux was present in 49 of 113 horses (43.4%) and was significant (> or = 21) in 32 (28.3%) horses. The recurrence rate was 13/161 (8.1%). Thirteen horses (13/174, 7.5%) had other lesions including small intestinal obstruction (4), 360 degrees large colon torsion (5), gastric rupture (2), thromboembolic colic (1) and small colon infarction (1). Of 115 cases, in 107 horses treated by surgery alone, 2 horses required a large colon resection, and 8 (8/107, 7.5%) horses died or were subjected to euthanasia. Twenty-six of 35 horses (74%) were successfully corrected by rolling under general anesthesia and, of the 9 horses taken to surgery after rolling, 4 had other lesions and 2 were corrected at surgery. Phenylephrine was used in 20 of 35 horses that were rolled and 2 horses required surgery after rolling with phenylephrine. Five horses were jogged after phenylephrine administration and all were successfully corrected. Eleven horses presented with the left colon located between the spleen and the body wall were treated successfully by fasting and/or i.v. fluids. One horse had a gastric rupture after rolling. The overall success rate was 92.5%. In conclusion, NSE is a condition associated with a good prognosis for medical or surgical correction. A small number of horses may have additional gastrointestinal lesions, which may affect outcome.

Neuroscience nursing practice in a new millennium.

Neuroscience nursing practice in the 21st century is considered from two perspectives: 1) scope of care and roles within a collaborative interdisciplinary model of care; and 2) patient-focused care within the challenging health care system. The implications of illness trends for neuroscience nursing practice are discussed, as are the developing changes in the health care delivery system driven by economics. The article focuses on the futuristic role of disease management in shaping practice and the models for practice which will prevail in this new health care environment.

A primer of neuroanatomy and neurophysiology.

Understanding the neuroanatomical structures and their clinical correlations are essential to caring for the neuroscience patient. By actualizing normal structures and functions, the nurse will be able to recognize abnormal clinical manifestations. With such recognition, the nurse will be able to predict nursing care priorities.

Structural and immunological characterization of a biosurfactant produced by Bacillus licheniformis JF-2.

Bacillus licheniformis JF-2 produces a very active biosurfactant under both aerobic and anaerobic conditions. We purified the surface-active compound to homogeneity by reverse-phase C18 high-performance liquid chromatography and showed that it is a lipopeptide with a molecular weight of 1,035. Amino acid analysis, fast atom mass and infrared spectroscopy, and, finally, 1H, 13C, and two-dimensional nuclear magnetic resonance demonstrated that the biosurfactant consists of a heterogeneous C15 fatty acid tail linked to a peptide moiety very similar to that of surfactin, a lipopeptide produced by Bacillus subtilis. Polyclonal antibodies were raised against surfactin and shown to exhibit identical reactivity towards purified JF-2 lipopeptide in competition enzyme-linked immunosorbent assays, thus providing further evidence for the structural similarity of these two compounds. Under optimal conditions, the B. licheniformis JF-2 biosurfactant exhibits a critical micelle concentration of 10 mg/liter and reduces the interfacial tension against decane to 6 x 10(-3) dyne/cm, which is one of the lowest interfacial tensions ever reported for a microbial surfactant.

The role of partial cystectomy in the treatment of recurrent invasive bladder cancer following radiotherapy.

Seventeen patients with recurrent invasive bladder cancer following radical radiotherapy were treated by partial cystectomy. Thirteen patients required augmentation enterocystoplasty, using an ileal patch in 10 patients and large bowel in the others. After 4 years' follow-up, eight patients are alive and disease-free with good bladder function. Of the nine patients who died, six died from bladder cancer and three of these suffered local recurrences. Responsiveness to radiotherapy or tumour stage were not helpful in predicting local recurrences, but all patients who had this complication had anaplastic tumours. In selected patients this procedure offers an alternative to salvage cystectomy, especially where a urinary diversion may be inappropriate.

Surgery, chemotherapy and whole abdominal radiotherapy in the management of advanced ovarian carcinoma.

A pilot study on 35 women was performed to determine the feasibility of giving whole abdominal radiotherapy after surgery and chemotherapy for Stage III and IV ovarian adenocarcinoma. The planned duration of therapy was only 6 months from diagnosis. Chemotherapy consisted of four courses of cis-platinum 100 mg/m2 alternating every 10-12 days with four courses of methotrexate 300 mg/m2 and cyclophosphamide 500 mg/m2 followed by folinic acid rescue. Twenty-nine of 35 (83%) patients were shown at second look surgery after chemotherapy to have residual tumour deposits no more than 2 cm in diameter. The usual radiotherapy dose was 2400 cGy in 20 fractions over approximately 4 to 5 weeks, with kidney shielding, and was generally well tolerated. Three patients failed to complete radiotherapy, two because of progressive disease and one because of persistent nausea and vomiting. During radiotherapy the white blood count fell below 2.0 X 10(9)/litre in seven patients (26%), and in eight patients (30%) the platelet count fell below 75 X 10(9)/litre. However, the white blood count nadir of 1.5 X 10(9)/litre was reached by 1300 cGy and the platelet nadir of 45 X 10(9)/litre was reached by 1400 cGy and both then levelled or recovered despite continuing radiotherapy. The median follow up since diagnosis is 26 months. Four of 12 patients with no tumour detected at second look operation have relapsed compared with 13 of 15 patients who had detectable tumour. Toxicity of this multi-modality therapy was acceptable.

Increases in intracranial pressure from succinylcholine: prevention by prior nondepolarizing blockade.

Whether succinylcholine causes an increase in intracranial pressure (ICP) in patients with brain lesions is uncertain and, if increased ICP does occur, its pathophysiology remains unknown. The authors investigated both the effect of succinylcholine on ICP and its modification with prior neuromuscular blockade by measuring ICP (subarachnoid bolt) in 13 consecutive patients with brain tumors who received succinylcholine both before and after complete neuromuscular blockade with vecuronium. Anesthesia was induced with thiopental, 6 mg X kg-1 iv, and nitrous oxide, 70% in oxygen, while ventilation was controlled (PaCO2 = 37.2 mmHg +/- 1.7 SE). Succinylcholine, 1 mg X kg-1 iv, was administered and ICP, heart rate (HR), and blood pressure (BP) were recorded until normal twitch tension was restored. Complete neuromuscular blockade was then established with vecuronium, 0.14 mg X kg-1 iv; 3 min later, succinylcholine, 1 mg X kg-1 iv, was repeated. The resulting changes in ICP, HR, and BP were recorded for 3 min. Following the first dose of succinylcholine, mean ICP increased from 15.2 mmHg +/- 1.3 SE to 20.1 mmHg +/- 2.0 SE (P less than 0.05), with five of the patients sustaining increases in ICP of 9 mmHg or greater. In contrast, when succinylcholine was given after vecuronium-induced paralysis, no patient developed an increase in ICP greater than 3 mmHg (P less than 0.05 compared with the incidence of ICP greater than or equal to 9 mmHg observed after the first dose of succinylcholine). A second group of six patients received two doses of succinylcholine according to the same protocol but without an intervening dose of vecuronium.(ABSTRACT TRUNCATED AT 250 WORDS)

Renovascular hypertension following radiotherapy and chemotherapy treated by transluminal angioplasty.

A man aged 33 with poorly controlled hypertension who had been treated with radiotherapy and combination chemotherapy for testicular teratoma 8 years earlier was found on arteriography to have 75% stenosis of the left renal artery and occlusion of the right renal artery. The stenosis was dilated by transluminal angioplasty and the hypertension adequately controlled. Patients who develop high blood pressure after abdominal radiotherapy with or without chemotherapy should be investigated for renal artery stenosis.

Serum potassium following succinylcholine in patients with brain tumours.

Serum potassium levels were measured in 15 patients with brain tumours between 3-7 cm diameter, during thiopentone/70 per cent N2O in O2 anaesthesia, with mask ventilation controlled to maintain a constant end-tidal CO2 concentration. Potassium levels were determined one minute before and one and ten minutes after administration of succinylcholine 1.0 mg X kg-1 IV. No statistically significant increase in serum potassium occurred following succinylcholine, nor were there any ECG changes associated with succinylcholine administration. Use of succinylcholine in patients with brain tumours does not appear to cause elevation of serum potassium levels or ECG changes.

Intracranial pressure after atracurium in neurosurgical patients.

In order to investigate the usefulness of atracurium for neurosurgical anesthesia, we studied its impact on intracranial pressure (subarachnoid bolt) mean arterial pressure (radial artery catheter) and cerebral perfusion pressure (mean arterial pressure-intracranial pressure) in 20 patients undergoing elective craniotomy for brain tumor excision. General anesthesia was induced with thiopental, 4 mg/kg intravenously, and maintained with 70 percent nitrous oxide in oxygen. Ventilation was controlled by face mask, with end-tidal CO2 held constant. Once intracranial pressure and mean arterial pressure had stabilized, the response to atracurium, 0.5 mg/kg intravenously, was continuously recorded for 5 min in 10 patients. An additional 10 patients received no atracurium and served as matched controls. Thiopental caused reductions in ICP in both groups of patients. Comparing the responses of the patients who received atracurium with those who did not, we found that atracurium had no significant effect on intracranial pressure, mean arterial pressure or cerebral perfusion pressure. Based on these data we conclude that atracurium appears to be preferable to the other available neuromuscular blocking agents that have been evaluated for neurosurgical anesthesia.

Adriamycin alone or combined with vincristine in the treatment of advanced breast cancer.

One hundred and nineteen women with advanced breast cancer treated previously by endocrine therapy but no prior chemotherapy were given adriamycin 70 mg/m2 i.v. on day 1 of a 3-weekly cycle for 8 courses, followed by a regimen of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) until relapse. They were allocated randomly to receive either no treatment (group A) or vincristine 1.4 mg/m2 i.v. on days 1 and 8 during treatment with adriamycin (group AV). In 107 evaluable patients objective responses were seen in 30/53 patients (57%) in group A and in 28/54 patients (52%) in group AV. The projected dose of adriamycin received was 78% in group A and 75% in group AV; and 60% for vincristine in group AV. The subjective and haematological toxicity for adriamycin was similar in both groups, but 65% of patients treated with vincristine developed neurotoxicity. The median duration of objective regressions was the same for both groups (7 months), and the median time to failure was 5 months for group A and 6 months for group AV respectively. The median survival of the responders tended to be longer in group AV (17.5 months) than in group A (13 months), but this difference was not statistically significant (P = 0.112). It is concluded that there is no advantage therapeutically in combining vincristine and adriamycin in patients with advanced breast cancer.

Contribution of prednisolone to the primary endocrine treatment of advanced breast cancer.

Two hundred and four patients with progressive locally advanced or metastatic breast cancer not controllable by local therapy alone, and who had had no prior systemic therapy for advanced disease, were treated by primary endocrine therapy according to menopausal status. Premenopausal patients received ovarian irradiation (O) whilst postmenopausal patients received tamoxifen 10 mg b.d. (T). Patients were randomised to receive either no additional treatment or prednisolone 5 mg b.d. (P). In 180 evaluable patients, T + P induced significantly more responses than T alone (26/73 vs 9/72, P less than 0.01) and the addition of P to O in premenopausal patients also induced more responses than O alone (7/16 vs 4/19), but this difference was not significant and accrual of premenopausal patients continues. There was a trend for patients receiving T + P to have a longer survival than those receiving T alone (median 25 vs 16 months). These trends occurred in patients with tumours positive for oestrogen receptors and when receptor status was unknown; patients with receptor-negative tumours had a negligible response to endocrine treatment. P mitigated the occurrence of hypercalcaemia and tumour flare sometimes seen with T alone.

Regulation by catecholamines of spontaneous growth hormone secretion in the baboon.

To gain an increased understanding of the role of central neurotransmitters in the regulation of spontaneous growth hormone (GH) secretion in the primate, we investigated the effects of peripheral intravenous infusion of the alpha-adrenergic receptor-blocking agent, phentolamine (5.0-mg bolus and 1.5 mg . kg-1 . 12 h-1), and the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (MPT, 300 mg . kg-1 . 24 h-1), on the pattern of GH secretion in five adolescent male baboons. Serum GH concentrations were measured in blood samples taken at 20-min intervals over 12 h (0530-1730) after an overnight fast. In nontreatment control studies, GH secretion exhibited a predictable rhythmic oscillation with a mean period of 5.7 +/- 0.4 (SE) h. Phentolamine significantly decreased the 12-h mean and integrated GH concentrations compared to control values, but the small peaks of GH, which could be distinguished from base-line concentrations in three of the animals, occurred at the same time as during control studies. Whereas alpha-methyl-p-tyrosine slightly reduced serum levels of GH, it significantly increased the GH pulse frequency in the baboons. A two- to fourfold increase in serum prolactin levels occurred in all animals treated with MPT. These findings suggest that alpha-adrenergic pathways play a stimulatory role in maintaining spontaneous daytime GH secretion in the baboon and that one or more catecholamines are involved in the generation of rhythmic GH release.

Corticosteroids for elderly patients with breast cancer.

Ninety-one assessable elderly women (greater than 65 years) with advanced breast cancer were treated with prednisolone 15 mg (or cortisone 75 mg) daily after primary endocrine treatment (estrogens, androgens or tamoxifen). Thirteen (14%) achieved an objective regression, and 19 (21%) others showed no change for greater than or equal to six months. Hence, 32 patients (35%) had control of disease for about one year. Responses were mainly in soft tissue and skeletal lesions and were independent of response to prior endocrine treatment. Toxicity was low. Low-dose corticosteroid treatment is of value in controlling advanced breast cancer in elderly women.