Quality of care: a brief history and a look ahead.
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Biomedical subjects
Publications and source records attributed to J Bruce.
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BACKGROUND: An outbreak of legionnaires' disease occurred in central London in January and February 1989. An Infection Control Committee was established to investigate the outbreak and institute control measures. The objective of this paper is to describe the investigation and control of the outbreak. METHODS: An epidemiological survey and case-control study were carried out. The subjects were cases of community acquired pneumonia associated with central London with onset of illness in January and February 1989. RESULTS: Thirty-three confirmed cases, including five deaths, and ten suspected cases, including three deaths, were identified with dates of onset from 1 January to 11 February. A clustering of visits by cases to the vicinity of Piccadilly Circus was noted, and a case-control study demonstrated a strong association between illness and visits to this area in the two weeks before onset of symptoms. The causative organism, Legionella pneumophila serogroup 1, was isolated from six patients. Legionella pneumophila of the same serogroup was isolated from water samples from five wet cooling systems (cooling towers) in the area under investigation, but in only two systems was the organism indistinguishable by subtyping from the patients' strains. Many of the cooling towers examined were inadequately maintained, including one of the two above a building adjacent to Piccadilly Circus from which a strain indistinguishable from the outbreak strain was isolated. All cooling towers in the area were shut down until inspected, and only allowed to restart after appropriate maintenance had been instigated. CONCLUSIONS: This outbreak showed the continuing risk of legionnaires' disease posed by wet cooling systems, including cooling towers, and highlighted the need to assess this risk so that appropriate maintenance is carried out. Regulations have recently been introduced, under the Health and Safety at Work Act, requiring notification of all wet cooling systems to the local authority to facilitate the investigation of outbreaks of legionnaires' disease.
The present study is the first report of the epidemiological survey carried out as a part of the Praziquantel resistance project which is one of the projects of Schistosomiasis Research Project (SRP) in Egypt. The results of the study, which has been carried out in 3 villages, revealed that praziquantel is effective as an antischistosomal drugs and reduced egg count significantly. However at the end of the study some cases remained infected in spite of the three treatment regimens. Several factors can be responsible, among them is the presence of resistance strains, which will only be elucidated in the subsequent steps of the project, when identification of resistant strains in experimental animals will be carried out.
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The use of hydrazine to release unreduced N- and O-linked oligosaccharides from glycoproteins has been investigated using several "standard" glycoproteins of previously defined glycosylation. It is shown that hydrazinolysis can be used to release intact N- and O-linked oligosaccharides in an unreduced form. The release of O-linked oligosaccharides occurs with a lower temperature dependence than the release of N-linked oligosaccharides, and the kinetic parameters governing release of oligosaccharides from these standard glycoproteins have been determined. These parameters allow a definition of reaction conditions under which anhydrous hydrazinolysis can be used to selectively release O-linked oligosaccharides (60 degrees C, 5 h) or release both N- and O-linked oligosaccharides (95 degrees C, 4 h) in high yield (> 85%) from all glycoproteins investigated (n = 11). Under these reaction conditions, the recovered N- and O-linked oligosaccharides are structurally intact (as judged by 600-MHz 1H-NMR, laser-desorption mass spectrometry, HPAEC-PAD, gel filtration, and glycosidase digestion), with the possible exception of certain N- and O-acyl substituents of sialic acid. This use of mild hydrazinolysis therefore allows both the simultaneous and sequential chemical release from glycoproteins of O- and N-linked oligosaccharides in their intact unreduced form.
The light (NF-L), mid-sized (NF-M) and heavy (NF-H) neurofilament (NF) genes were probed with methylation-sensitive restriction enzymes and patterns of methylation and expression of the NF genes were compared in tissues and cell lines of the mouse. The 5' regions of all three NF genes are identified as CpG islands that remain unmethylated in expressing and non-expressing tissues, although partial methylation occurs at -795 in NF-H and at -525 in NF-M. Methylation of the NF CpG islands is associated with the inactivation of NF genes in L cells and with the selective inactivation of NF-L and NF-M in Neuro 2a cells. We also show that methylation diminishes the ability of the NF promoters to drive transcription of a CAT reporter gene. Hence, the presence of CpG islands may be important in determining patterns of NF transcription in vitro. Moreover, the preservation of CpG islands may be an evolutionary link that bears upon the nature of the NF genes and the mechanisms that have evolved to limit NF expression.
Oesophageal duplication cysts in infants (usually males) should be recognized as a cause of respiratory distress which worsens during the neonatal period, and which is associated with feeding difficulties. Their radiological appearance is that of a right-sided posterior mediastinal mass, which is shown to be cystic on ultrasound. Excision is curative.
A patient with an accessory right diaphragm discovered during thoracotomy for correction of severe thoracolumbar scoliosis is presented to illustrate the diagnostic difficulties that may occur in children with accessory diaphragm. The patient had presented at an early age with respiratory symptoms which were assumed to be asthmatic in aetiology and complicated by progressive chest deformity. The respiratory symptoms in accessory diaphragm can be improved by surgery.
The levels of light, mid-sized, and heavy neurofilament (NF) mRNAs were compared to that of beta-actin mRNA in primary dissociated cultures of adult rat dorsal root ganglia (DRG). Decreases in the levels of all three NF mRNAs occur after 24 h in culture, mimicking the down-regulation of NF mRNAs in axotomized DRG neurons. The loss of NF mRNAs in DRG cultures is prevented by actinomycin and, to a lesser extent, by cycloheximide. Based on decay curves in actinomycin-treated cultures, the half-lives of NF mRNAs are at least 4 days in DRG neurons, but < 24 h in PC12 cells. Our data support the view that NF mRNAs are stabilized in DRG neurons and that stabilization prevents destabilization by a transcription-dependent process. We further propose that putative stabilizing factor(s) are able to prevent degradation of NF transcripts in intact neurons, but not in axotomized or cultured neurons.
We describe a 33-year-old homosexual man with a steroid-responsive, remitting and relapsing leukoencephalopathy associated with recent human immunodeficiency virus type 1 (HIV-1) seroconversion. Biopsy of a parieto-occipital lesion revealed demyelination and astrogliosis with focal necrosis. Detailed investigations demonstrated no pathogens in the brain other than HIV-1. This patient illustrates that a neurological disorder clinically indistinguishable from multiple sclerosis may be the presenting manifestation of HIV-1 infection and may occur in the absence of clinically significant immunosuppression.
We have cloned and examined the 5' flanking regions of the heavy (NF-H), light (NF-L) and mid-sized (NF-M) mouse neurofilament (NF) genes in order to begin to characterize the regions of each gene that regulate NF transcription. Chimeric plasmids bearing the CAT reporter gene and deletion mutants of the upstream NF genes were transiently transfected into neuronal (PC12 and Neuro 2A) and non-neuronal (HeLa) cell lines. Constructs bearing upstream regions to -4000 in NF-H, to -5600 in NF-L and to -4500 in NF-M were expressed at low levels in neuronal and in non-neuronal cells. Progressive deletion of 5' flanking sequence to -385 in NF-H, to -325 in NF-L and to -505 in NF-M caused a several-fold increase of transcription from the transfected plasmids. Increases of transcription by deletion mutants followed a similar pattern in neuronal and in non-neuronal cell lines. Negative upstream regions are located between -1314 and -385 in NF-H, between -936 and -325 in NF-L and between -874 and -505 in NF-M. Additional negative regions are present further upstream in NF-L and in NF-H. The negative regions of NF-H and of NF-L suppress transcription when placed in either orientation in front of the SV40 or a heterologous NF promoter. These studies demonstrate that the three mouse NF genes possess similar functional features, namely, that of a relatively strong and promiscuous promoter with negative upstream elements. The role of the negative elements in regulating NF expression remains unclear.
An outbreak of Salmonella dublin infection occurred in England and Wales in October to December 1989. Forty-two people were affected, mainly adults, and most lived in south-east England. Microbiological and epidemiological investigations implicated an imported Irish soft unpasteurized cows' milk cheese as the vehicle of infection. A case-control study showed a statistically significant association between infection and consumption of the suspect cheese (p = 0.001). Salmonella dublin was subsequently isolated from cheeses obtained from the manufacturer's premises. Initial control measures included the withdrawal of the cheese from retail sale and a Food Hazard Warning to Environmental Health Departments, as well as a press release, from the Department of Health. Subsequently, a decision was taken by the manufacturer to pasteurize milk used in the production of cheese for the UK market and importation of the cheese resumed in June 1990.
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Continent cutaneous diversions with a urinary reservoir emptied by clean intermittent self-catheterisation (CISC) using a non-refluxing conduit--the Mitrofanoff principle--were carried out in 10 children. Their age range was 3.9 to 17.1 years (average 12.2). The underlying diagnoses were ectopia vesicae (7), myelodysplasia (2) and a cervical cord injury secondary to birth trauma (1). The indications were incontinence secondary to poor bladder neck resistance in 8 children and an inaccessible urethral orifice in 2. The catheterising conduits used were the appendix in 9 and a vascularised gastric tube in 1. Eight children are bone-dry with CISC. Another child needed a reoperation following dehiscence of her bladder neck closure. The other child has an intact bladder neck and urethra and occasionally leaks overnight. Mitrofanoff diversions are a reliable means of continence with CISC. This means of urinary diversion can be permanent or temporary in children who cannot or will not catheterise urethrally. Elective appendicectomy in children with potential urinary incontinence or complicated urogenital anomalies is not recommended.
1. Induction of hypothyroidism in rats by feeding propylthiouracil (PTU) significantly increased serum cholesterol concentrations, and the effect was more pronounced for cholesterol in low-density lipoproteins (LDL) rather than high-density lipoproteins (HDL). The concentrations of serum triacylglycerol were decreased in hypothyroidism. These effects on serum lipids were also seen when the normal rats were pair-fed with the PTU-treated group. 2. Feeding a diet rich in saturated fat and cholesterol further increased cholesterol concentrations in LDL and also elevated that in very-low-density lipoprotein (VLDL) of hypothyroid rats. In euthyroid rats such a diet resulted in a relatively small increase in VLDL cholesterol, whereas LDL cholesterol was decreased. 3. Steady-state concentrations of mRNA for the hepatic LDL receptor were significantly decreased in the livers of hypothyroid rats, but were not significantly changed by high-fat feeding in euthyroid or hypothyroid rats. 4. The expression of the LDL receptor in hepatocytes cultured from hypothyroid rats was decreased relative to the euthyroid controls. 5. Whereas the esterification of cholesterol with oleate in hepatocytes cultured from hypothyroid rats was decreased, the activity of acyl-CoA:cholesterol acyltransferase (ACAT) in the livers of these animals was not changed. 6. High-fat feeding increased the hepatic ACAT activity in normal and hypothyroid rats. 7. Incubation of rat hepatocytes with 10 nM-tri-iodothyronine for 4 h increased the relative concentration of the mRNA for the LDL receptor by 25%. 8. It is therefore concluded that thyroid hormones stimulate the synthesis and expression of the hepatic LDL receptor. Elevated cholesterol concentrations in LDL in hypothyroidism probably result from a primary defect in the expression of the hepatic receptor, rather than indirectly via changes in ACAT activity.
In August 1988 an increase was noted in the number of cases of cryptosporidiosis identified by the microbiology laboratory at Doncaster Royal Infirmary. By 31 October, 67 cases had been reported. Preliminary investigations implicated the use of one of two swimming pools at a local sports centre and oocysts were identified in the pool water. Inspection of the pool revealed significant plumbing defects which had allowed ingress of sewage from the main sewer into the circulating pool water. Epidemiological investigation confirmed an association between head immersion and illness. The pools were closed when oocysts were identified in the water and extensive cleaning and repair work was undertaken. The pool water was retested for cryptosporidial oocysts and found to be negative before the pool reopened.
Between November 1988 and January 1989, a total of 155 people in 36 reported outbreaks suffered gastrointestinal symptoms associated with eating Stilton cheese, produced from unpasteurized cow's milk in the English midlands. Symptoms were suggestive of a staphylococcal illness but extensive laboratory testing of cheeses implicated in several of the outbreaks failed to detect any pathogen, toxin or chemical. Control measures were implemented, and included a voluntary withdrawal of the implicated Stilton cheese from sale on 23 January 1989 and a subsequent decision to use pasteurized milk in production of the cheese.