Overwhelming gram negative septic shock in haemochromatosis.
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Adult↗
Biomedical subjects
D Stewart
Publications and source records attributed to D Stewart.
Diagnostic exercise: ataxia and incoordination in ferrets.
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Aleutian Mink Disease↗
An assessment of antibiotic therapy of urinary tract infection in elderly, hospitalised patients.
The aim of the study was to compare the antibiotic treatment actually received by elderly, hospitalised patients with urinary tract infection (UTI) with 'optimal' therapy (as gauged by compliance with antibiotic policy, infecting organism, sensitivity data, patient renal function and cost). UTI was more common in females and in catheterised patients and E.Coli was the commonest pathogen. Trimethoprim and co-amoxiclav were the drugs used most frequently for either empirical or sensitivity data-based treatment. In 96% of infections a drug with appropriate action was administered. Often, however, treatment could have been optimised by substituting a cheaper suitable antibiotic, by standardising duration of therapy and ensuring that doses were adjusted for renal impairment. Savings from the use of 'optimal' therapy were estimated at 17%. There is clearly considerable scope for positive input from the clinical pharmacist in this area.
Aged↗
Sleep apnea in CAPD.
Sleep disturbances are common complaints of dialysis patients, and sleep studies have suggested that sleep apnea may occur frequently. We performed sleep studies on 18 stable continuous ambulatory peritoneal dialysis (CAPD) patients. Our results indicate that 6 of 18 patients (33%) had a respiratory disturbance index (RDI) greater than 15, which indicates severe sleep apnea. Twelve of 18 patients (67%) had an RDI greater than 5, indicating clinically significant sleep apnea. These results suggest that sleep apnea is common in CAPD patients. The impact of sleep apnea on the patients' quality of life remains to be determined.
Aged↗
Double-blind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer.
Patients receiving chemotherapy for metastatic breast cancer are at high risk of thromboembolic disease. Long-term oral anticoagulant therapy is needed but increases the risk of haemorrhagic complications. We have assessed the safety and efficacy of warfarin in very low doses as prophylaxis. Women receiving chemotherapy for metastatic breast cancer were randomly assigned either very-low-dose warfarin (152 patients) or placebo (159). The warfarin dose was 1 mg daily for 6 weeks and was then adjusted to maintain the prothrombin time at an international normalised ratio (INR) of 1.3 to 1.9. Study treatment continued until 1 week after the end of chemotherapy. The average daily dose from initiation of titration was 2.6 (SD 1.2) mg for the warfarin group and the mean INR was 1.52. The mean time at risk of thrombosis was 199 (126) days for warfarin-treated patients and 188 (137) days for placebo recipients (p = 0.45). There were 7 thromboembolic events (6 deep-vein thrombosis, 1 pulmonary embolism) in the placebo group and 1 (pulmonary embolism) in the warfarin group, a relative risk reduction of about 85% (p = 0.031). Major bleeding occurred in 2 placebo recipients and 1 warfarin-treated patient. There was no detectable difference in survival between the treatment groups. Very-low-dose warfarin is a safe and effective method for prevention of thromboembolism in patients with metastatic breast cancer who are receiving chemotherapy.
Antineoplastic Agents↗
Retrovirus-mediated gene transduction into canine peripheral blood repopulating cells.
Genetically marked peripheral blood progenitor cells were used to investigate their contribution to long-term hematopoietic reconstitution after autologous marrow and peripheral blood cell transplantation. After autologous marrow harvest and cryopreservation, canine peripheral blood progenitor cells were mobilized in three dogs by treatment with recombinant canine stem cell factor for 8 days. Peripheral blood mononuclear cells were collected and enriched for major histocompatibility complex (MHC) class II antigen-positive cells by avidin-biotin immunoadsorption, thereby enriching for repopulating cells. Subsequently, the cells were cocultivated for 24 hours on irradiated vector-producing packaging cells (PA317/LN), followed by an 11-day incubation in a vector containing long-term marrow culture system. On the day of transplantation, the animals were irradiated with 9.2 Gy total body irradiation (TBI), and transduced peripheral blood cells and untransduced cryopreserved marrow cells were infused within 2 hours of TBI. All three dogs engrafted. Two dogs are long-term survivors showing intermittently G418-resistant marrow-derived colony-forming unit granulocyte-macrophage colonies at a median of 1% and 2%, respectively (range, 1% to 10%), for now up to 48 weeks after transplantation. Neo-specific sequences were detected by polymerase chain reaction in peripheral blood granulocytes for now up to 65 weeks and in peripheral blood lymphocytes for up to 75 weeks after transplantation. Peripheral blood samples of the dogs were free of helper virus and no side effects from the transduction were observed. One of the three dogs died from chronic canine distemper sclerosing encephalitis on day 84, whereas the other two dogs are alive at 15 and 17 months. Our data show successful retroviral transduction of canine peripheral blood repopulating cells. Long-term persistence of marked myeloid and lymphoid cells after transplantation suggests that peripheral blood contains repopulating cells that contribute to long-term hematopoietic reconstitution after otherwise lethal TBI.
Animals↗
Phase II study of elsamitrucin in non-small cell lung cancer.
Elsamitrucin (BMY-28090) a novel fermentation product has demonstrated pre-clinical anti-tumour activity against a number of cell lines. The dose limiting toxicity in phase I studies was a reversible increase in hepatic transaminase. This study was initiated to determine the activity of elsamitrucin in patients with previously untreated, bi-dimensionally measurable, cytologically or histologically proven, non-small cell lung cancer who were not curable by surgery. Elsamitrucin at a dose of 25 mg/m2 was administered intravenously over 5-10 min weekly for a minimum of 6 weeks. Seventeen patients were entered on study, 15 were evaluable for toxicity and 14 evaluable for response. No responses were documented in the 14 patients evaluable for response. Both hematological and non-hematological toxicities were mild to moderate in severity. The commonest being nausea, vomiting, lethargy and local skin reactions at the site of the infusion. These results indicate that elsamitrucin when given in this dose and schedule to patients with surgically incurable non-small cell lung cancer has no activity.
Aged↗
Enterococcal bacteraemia: a prospective study of 125 episodes.
One hundred and twenty-five episodes of enterococcal bacteraemia occurring over a 50-month period were studied prospectively. Enterococcus faecium was the commonest species, accounting for 76 (59.8%) of the 127 isolates. Overall, 33.1% of isolates were resistant to ampicillin and one isolate (0.8%) to vancomycin; high-level gentamicin resistance was detected in 4.3% of 93 isolates tested. The percentage of nosocomial episodes was 70.4, and 95.2% of the patients had significant underlying illness. Central venous catheters (CVCs) were the commonest source of infection. Eighty-four per cent of episodes were ultimately treated with appropriate antibiotics. The overall mortality rate was 17.6%, and that directly attributable to infection was 8.0%. An increased mortality rate was observed in intensive care and neonatal unit patients, and in patients who had received antimicrobial therapy in the 2 weeks prior to enterococcemia. CVC-related infections were associated with a reduced mortality. No other clinical or microbiological factors were found to influence outcome.
Ampicillin Resistance↗
Intraoperative facial nerve monitoring: a description of a unique system.
Intraoperative facial nerve monitoring has become an integral adjunct in facial nerve identification and preservation for patients undergoing cerebellopontine angle surgery. Since the first description of EMG monitoring of facial nerve activity intraoperatively, many systems have been developed. These systems often rely on unilateral monitoring of the facial nerve with auditory feedback to the surgeon, and it is difficult to distinguish between artifact and significant stimulation of the facial nerve. In this paper, we present the use of a bilateral, multialarm, facial nerve monitoring system that has multiple advantages over previous systems. Furthermore, we review our experience with this bilateral system, comparing a group of 50 monitored patients to a group of 50 unmonitored patients.
Adolescent↗
The prevention of spinal injuries in rugby football.
The incidence of injuries to the spinal cord sustained at rugby in South Africa, New Zealand and Australia is reviewed. Ninety-seven injuries seen at Stoke Mandeville Hospital at the National Spinal Injuries Centre (NSIC) between 1956 and 1993 are analysed in detail. There were 93 accidents at rugby union, two at American football and two at rugby league. The injuries were of the cervical spine apart from four hysterics and one thoracic injury. The thoracic injury occurred after the game when the player fell downstairs. The injuries were analysed according to the mechanism of injury, the neurological condition, the causation, the standard of the player and the position in the field. The injuries caused were the result of force being applied to the skull which was transmitted to the cervical spine resulting in injury to the cervical cord. As a result of this research, representations were made to the appropriate authorities and changes in the laws were made. As a result of these law changes there has been a dramatic reduction in the overall number of injuries and the elimination of the injury from the loose scrum. This paper discusses the historical sequence of how these preventative measures came about to reduce the incidence of injuries and the legal implications whereby the authors took part in two law suits. The legal consequences are analysed in detail.
Adolescent↗
Response surface analysis of bioconcentration by chlorinated organics using molecular connectivity.
Bioconcentration data for chlorinated organic compounds is analyzed in a response surface technique using molecular connectivity indices to represent the molecular structure of the compounds. The response surface method is described and applied to this data set. The model uses the zero order chi indices, 0 chi and 0 chi v, as the variables in a general two-dimensional parabolic equation. The statistical results suggest a good model for estimation of BCF values: [Formula: see text] The data set is analyzed further in terms of the sigma and delta chi zero indices: sigma x 0 = 0 chi + 0 chi v and delta x 0 = 0 chi - 0 chi v. These transformed chi indices are orthogonal and represent structure information in a useful manner. The sigma x 0 index encodes molecular size and the delta x 0 index encodes electronic features related to pi and lone pair electrons. The structure information in the data set is analyzed in terms of these significant structure features. The data are presented in the form of a contour plot which facilitates analysis and indicates the maximum BCF for this data set.
Chlorophenols↗
Gemcitabine is an active new agent in previously untreated extensive small cell lung cancer (SCLC). A study of the National Cancer Institute of Canada Clinical Trials Group.
BACKGROUND: The new pyrimidine antimetabolite Gemcitabine has shown preclinical efficacy in a number of solid tumour lines and acceptable toxicity in phase I trials. As part of an ongoing effort to identify active new agents in small cell lung cancer, the NCIC Clinical Trials Group studied Gemcitabine in previously untreated patients with extensive disease. PATIENTS AND METHODS: Twenty-nine newly diagnosed patients with untreated extensive small cell lung cancer and at least one bidimensionally measurable site received Gemcitabine as a 30 minute intravenous infusion weekly x 3 every 4 weeks. The starting dose was 1000 mg/m2/week in the first 17 patients and 1250 mg/m2/week in the remainder. Patients were reevaluated for response every 4 weeks. Those failing to respond after 2 cycles of therapy were to be offered standard chemotherapy. RESULTS: Of the 29 patients entered, all were evaluable for toxicity and 26 for response. One complete and 6 partial responses were seen giving a response rate of 27% (95% CI: 11%-47%). Median response duration was 12.5 weeks and the median survival of the entire population was 12 months. Toxic effects were mild to moderate: in particular serious myelosuppression was uncommon. CONCLUSIONS: Gemcitabine is active in previously untreated small cell lung cancer in doses which produce little toxicity. Combination studies of Gemcitabine with other agents active in this disease are warranted.
Aged↗
A community outbreak of echovirus infection associated with an outdoor swimming pool.
Forty-six people became ill with vomiting, diarrhoea and headache within days of an outdoor swimming pool opening for the summer season in a small seaside village. During the weekend of the outbreak, 185 tickets to the pool had been sold. It was found that 34 bathers were ill, and one subject had vomited into the pool. All other cases arose after this incident. The risk of infection was greatest among those who swallowed pool water (24/28 versus 10/17, p = 0.07). Echovirus 30 was isolated from the case who vomited into the pool and from six other cases. Normal chlorine levels had not been adequate to contain the infection risk from vomitus, and, in future, pool attendants witnessing such incidents should consider closing the pool to the public and seeking advice on superchlorination.
Adolescent↗
Angiotensin converting enzyme inhibition does not affect the response to exogenous angiotensin II in the human forearm.
Suppression of endogenous levels of angiotensin II by angiotensin converting enzyme inhibition, may result in up-regulation of vascular AT1 receptors. We have evaluated the effects of orally administered enalapril on angiotensin II induced vasoconstriction in the human forearm. Subjects received in random order, enalapril (20 mg) or matched placebo daily for 2 weeks. Forearm blood flow response to increasing doses of angiotensin II was measured using venous occlusion plethysmography at the beginning of the study and at the end of each 2 week treatment period. Treatment with enalapril significantly reduced plasma angiotensin II levels and supine blood pressure compared with placebo. The percentage reductions in forearm blood flow in the infused arm, in response to the maximum dose of angiotensin II (50,000 fmol min-1) were 48.1 +/- 3.6% at baseline, 57.5 +/- 3.6% on placebo and 54.5 +/- 4.2% on enalapril. The differences were not significantly different. This demonstrates that suppression of plasma angiotensin II for a 14 day period does not enhance the response to exogenous intra-arterial angiotensin II in the human forearm of healthy salt replete subjects.
Administration, Oral↗
The HLA-B73 antigen has a most unusual structure that defines a second lineage of HLA-B alleles.
The nucleotide sequence of cDNA encoding the HLA-B73 antigen was determined; it is unusually divergent, differing from other HLA-B alleles by 44-77 nucleotide substitutions. Features that distinguish the B*7301 heavy chain from other HLA-B heavy chains include multiple substitutions in the alpha 3 domain and a duplication-deletion within the transmembrane region that increases the length of B*7301 compared to other HLA-B heavy chains. The duplication-deletion is shared with subsets of B alleles from the homologous gorilla (Gogo-B) and chimpanzee (Patr-B) loci. Other unusual features of B*7301 are individually shared with certain alleles of the HLA-A, HLA-C, HLA-F, Gogo-B and Patr-B loci. The B*7301 molecules has sequence elements in common with members of the B7 crossreacting group in the alpha 1 domain and is shown to possess the ME1 epitope, which is held in common with the B7, B22, B27, B42 and B67 antigens. B*7301 has a unique cysteine at position 270 of the alpha 3 domain which appears accessible but probably does not form disulphide-bonded B*7301 dimers in cell membranes. B*7301 represents a newly discovered but ancient lineage of HLA-B alleles that appears poorly represented in the modern human population.
Alleles↗
Living wills: would sick people change their minds?
Patients admitted acutely to a geriatric medical unit were interviewed on admission about their opinions on cardiopulmonary resuscitation (CPR). They underwent a general examination and their mental health was documented by completing the geriatric depression scale. Those who did not wish CPR in the event of a cardiac arrest were questioned again on recovery. Of 216 patients admitted, only three objected to answering the questions and after the other exclusion criteria were applied, 100 patients were included in the study. A total of 92% of patients wished CPR in the event of a cardiac arrest. The 8% who did not wish CPR contained more people scoring high on the geriatric depression scale. After recovery, three of that eight had changed their minds and wished CPR if required. Patients who are acutely unwell may make decisions that are influenced by their condition at this point in time and it is important to recognize that these decisions may not be maintained. In this study, consultant geriatricians did not reflect their patients' desires in making decisions about who should receive CPR if required.
Acute Disease↗
Effect of mouthwashes of variable NaF concentration but constant NaF content on oral fluoride retention.
Previous work showed that oral fluoride levels increased with increasing applied F dose for both mouthwashes and dentifrices. This study aimed to determine whether the above dependence was related to applied fluoride concentration or applied fluoride amount. Ten adults mouthrinsed with aqueous NaF solutions of 1-10 ml, each of which contained 2.5 mg F, i.e. in the concentration range 250-2,500 ppm F. Subjects rinsed for 1 min and then spat out. Samples of mixed saliva were collected for 3 h afterwards, which were analysed for fluoride. Salivary fluoride clearance curves were obtained which could be fitted to a pharmacokinetic model involving processes ascribed to loss of fluoride from saliva by swallowing and to exchange of fluoride between saliva and an oral reservoir. Mean salivary fluoride concentrations increased significantly with increasing applied F concentration both within the first 3 h after single use and up to at least 18 h after regular daily use. These findings suggest that applied F concentration is a more important factor than applied F amount per se in determining the elevation of oral fluoride levels following topical fluoride use. This implies that application of a given F dose, in a smaller volume at higher concentration than the current norm, may increase efficacy without increasing the risk of adverse effects.
Adult↗
Central sleep apnea is associated with increased ventilatory response to carbon dioxide and hypersecretion of growth hormone in patients with acromegaly.
Although obstructive sleep apnea (OSA) occurs commonly in acromegaly, we have recently reported an unexpectedly high prevalence of central sleep apnea (CSA) in these patients. Acromegalic patients with CSA have increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels compared with their counterparts with OSA. Studies in animals, normal humans, and patients with sleep apnea have suggested that CSA is associated with increased gain of the respiratory control system. To examine the relationship between sleep apnea, respiratory control, and hormonal activity in acromegaly, we performed sleep studies and examined ventilatory responses to hypoxia at resting CO2 (HVR) and 8 mm Hg above resting CO2 (HHVR) and hypercapnia (HCVR) in 54 patients with acromegaly who also underwent detailed endocrine evaluation. Patients with CSA (n = 11) had higher HCVR (3.47 +/- 0.57 L/min/mm Hg) than did patients with obstructive sleep apnea (OSA) (1.86 +/- 0.19, n = 33) and patients without sleep apnea (1.77 +/- 0.21, n = 10). Measures of ventilatory control were all correlated with the mean of 12 hourly GH concentrations, but only HCVR was correlated with IGF-1 levels. Multiple linear regression analysis revealed that HCVR, HHVR, and IGF-1 could explain 39% of the variability in the degree of CSA in acromegalic patients with sleep apnea. We conclude that increased ventilatory responsiveness and elevated hormonal parameters of disease activity both contribute to the pathogenesis of central sleep apnea in acromegaly.
Acromegaly↗