Developing clinical guidelines for the management of patients with stroke. Scottish Intercollegiate Guidelines Network (SIGN).

Clinical guidelines on the management of stroke have been developed for national use in Scotland. The guidelines were developed by the Scottish Intercollegiate Guidelines Network (SIGN) which was established by the Conference of the Royal Colleges and their Faculties in Scotland to sponsor and support the development of National Guidelines on a multi-professional basis.

Predictive assessment of vocal efficiency (PAVE). A method for voice therapy outcome measurement.

A prospective study was carried out to examine the degree to which a standard voice assessment could discriminate between the potential benefits of two different voice therapy programmes for individual patients. The study encompassed 200 dysphonia subjects who were referred for voice therapy and had completed treatment within a prescribed two-year period. A standard assessment procedure was carried out on first attendance for each patient and guidelines were used to assign patients to different treatment programmes on the basis of the assessment results. The assessment discriminated well between patients requiring voice therapy to change physiological parameters of voice usage and patients able to self adjust voice usage, and provided an objective means of measuring outcomes.

Efficacy of control measures in preventing nosocomial transmission of multidrug-resistant tuberculosis to patients and health care workers.

OBJECTIVE: To assess the efficacy of control measures in decreasing nosocomial transmission of multidrug-resistant tuberculosis. DESIGN: Retrospective cohort study. SETTING: A teaching hospital in New York City. POPULATION: 40 patients hospitalized with multidrug-resistant tuberculosis (case-patients) and health care workers receiving tuberculin skin testing. INTERVENTIONS: Centers for Disease Control and Prevention (CDC) 1990 guidelines for preventing transmission of tuberculosis, including 1) prompt isolation and treatment of patients with tuberculosis; 2) rapid diagnostic techniques for processing Mycobacterium tuberculosis specimens; 3) negative-pressure isolation rooms; and 4) molded surgical masks for health care workers. MEASUREMENTS: Proportion of case-patients with nosocomially acquired tuberculosis and rate of tuberculin skin test conversion among health care workers before and after implementation of control measures. RESULTS: The proportion of patients with multidrug-resistant strains of M. tuberculosis decreased after the interventions (10 of 70 [14%] compared with 30 of 95 [32%] patients before the intervention; relative risk [RR], 0.5; 95% CI, 0.2 to 0.9). Before onset of multidrug-resistant tuberculosis, case-patients in the intervention period were as likely to be hospitalized on high-risk wards containing patients with tuberculosis (4 of 10 compared with 17 of 30 patients; RR, 0.7; P = 0.5) but were less likely to be exposed to another case-patient with tuberculosis (1 of 10 compared with 20 of 30 patients; RR, 0.2; P = 0.003). Tuberculin skin test conversion rates for health care workers assigned to wards housing patients with tuberculosis were lower in the intervention period than in the preintervention period (4 of 78 [5%] compared with 15 of 90 [17%] conversions; P = 0.02), decreasing to levels observed for workers assigned to other wards (4 of 78 [5%] compared with 9 of 228 [4%] conversions; P = 0.7). CONCLUSIONS: Implementing control measures reduced nosocomial transmission of multidrug-resistant strains to patients and health care workers.

Intrarenal cytokine mRNA expression and location in normal and IgA nephropathy tissue: TGF alpha, TGF beta, IGF 1, IL-4 and IL-6.

Peptide regulatory factors (PRFs) are critical components in the regulation of glomerular inflammatory response to immune injury and may also have a primary role in modulating intrinsic cell proliferation and matrix synthesis. Dysregulation of PRFs and glomerular infiltration with inflammatory, including mononuclear, cells occur in models of nephritis, but direct evidence for their role is not established in normal and diseased tissue in man. Using in situ hybridization techniques capable of detecting specific cellular messenger RNA we have evaluated normal human and IgA nephropathy diseased renal tissue for expression and location of PRF encoding mRNA. Permeabilized tissue was examined by autoradiography using 35S labelled-antisense, and -sense riboprobes for TGF alpha, TGF beta, IGF 1, IL-4, and IL-6 encoding mRNA. TGF beta was constitutively expressed in normal glomerular mesangium, capillary loop, Bowman's capsule, and vascular endothelial and tubular cells, but was downregulated in IgA nephropathy tissue. In contrasting and distinct patterns, TGF alpha encoding mRNA was found in neither tissue, whereas IGF 1 mRNA was expressed in normal and also in diseased tissue. IGF 1 mRNA activity was intense within tubular cell cytoplasm in normals, with similar characteristics in IgA nephropathy. Cytokines IL-4 and IL-6 mRNAs were absent in normals, with IL-4 detectable throughout renal substance in disease; IL-6 gene transcription was intense in glomerular and vascular endothelial sites in IgA nephropathy. These findings implicate selective gene induction and suppression in disease, suggesting functional downregulation of glomerular TGF beta, coincident with autocrine functions for IL-6 and IL-4 in the pathogenesis of IgA-related nephropathy.

Prevalence of canine distemper antibodies in the pagetic population.

Recent molecular evidence has implicated canine distemper virus (CDV) as a possible aetiologic agent in Paget's disease. However, previous serological studies have shown no differences in levels of anti-CDV antibodies between Paget's patients and controls. In this study, the technique of enzyme linked immunosorbent assay was used to measure anti-CDV antibodies in a group of Paget's patients from the North West of England. Some patients were undergoing treatment with 3-amino-hydroxypropylidene (APD), and the pre-treatment levels of antibody were compared with those following treatment. With several patients, it was also possible to compare the antibody levels with results from in situ hybridisation studies. No significant difference was found between the levels of anti-CDV antibodies in patients and controls. However, several patients and some of the controls did have markedly elevated levels of anti-CDV antibody. Antibody levels remained fairly constant following treatment with APD, except for two patients who showed marked changes. The patients positive for CDV by in situ hybridisation had significantly lower levels of anti-CDV antibodies when compared with those that were negative by in situ hybridisation. These results suggest that if CDV does cause Paget's disease, anti-CDV antibodies play little or no part in the disease pathogenesis. High levels of anti-CDV antibodies in both Paget's patients and controls suggest that a canine virus can infect humans. The fact that those patients that had CDV transcripts detectable in their bone cells had low levels of anti-CDV antibodies might suggest failure to clear the virus during an initial infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Paramyxoviruses and Paget's disease.

Using the technique of in situ hybridisation, we extended our initial studies of the occurrence of canine distemper and measles virus in Paget's disease. Bone samples from untreated patients and patients treated with 3-amino-hydroxypropylidene 1,1 bisphosphonate pamidronate (APD) were examined for canine distemper nucleocapsid (CDV-N), measles nucleocapsid (MV-N), respiratory syncytial virus fusion (RSV-F), and simian virus 5 haemoglutinin-neuraminidase (SV5-HN) sequences using 35S-labelled sense and antisense riboprobes. Only CDV-N mRNA was detected in osteoclasts, osteoblasts, and mononuclear cells. In untreated Paget's patients, 63.5% were found to have CDV sequences residing in bone cells, and 48.2% of those undergoing APD treatment were still found to have the viral sequences. RSV-F mRNA was only found in one patient. None of the other paramyxoviruses tested were detected. This study shows that CDV can infect a human host and may be an aetiological agent of Paget's disease of bone.

Canine distemper virus transcripts detected in the bone cells of dogs with metaphyseal osteopathy.

Using the technique of in situ hybridisation, we have recently extended our observations that canine distemper virus (CDV) is present in the bone cells of patients with Paget's disease, and have shown that CDV is also detectable in the bone cells of dogs that are naturally infected with the virus. Since hybridisation was localised to bone cells within the metaphyses of the affected dogs, we investigated the possibility that CDV might be involved in the canine metaphyseal bone disorder, metaphyseal osteopathy. Bone samples from three cases of metaphyseal osteopathy were examined for the presence of the CDV nucleocapsid (CDV-N) gene and the measles virus nucleocapsid (MV-N) gene, using 35S-labelled sense and antisense riboprobes. As with our previous findings in Paget's disease of bone, only the antisense probe was found to hybridize to the osteoblasts and osteoclasts within the affected metaphyses. No hybridisation was seen with the CDV-N sense and MV-N probes in any of the samples tested. Bone samples were also taken from one of the cases to check for the presence of the CDV-N gene using the polymerase chain reaction (PCR). Our findings with in situ hybridisation were confirmed by PCR and subsequent Southern blotting and probing with a 32P-labelled cDNA probe. The detection of CDV RNA within the bone cells of dogs with metaphyseal osteopathy suggests that this virus may be a cause of the disease and provides further, indirect evidence that CDV might be responsible for the bony abnormalities seen in Paget's disease of bone.

Canine distemper virus transcripts sequenced from pagetic bone.

Paget's disease is a chronic disease of the skeleton which is believed to be caused by a persistent virus of the paramyxovirus family. There is still conflict as to the precise identity of the virus(es) involved in causing this disease. Our previous results using in situ hybridisation have implicated distemper as a possible cause of this disease. In order to confirm these results, we have reverse transcribed RNA from pagetic bone and have specifically amplified for distemper and measles sequences using the polymerase chain reaction (PCR) technique. We have found that 8/13 of the patients examined had distemper and 1/10 cases had measles nucleic acids sequestered within their bone cells. One individual was found to have both viruses sequestered in his bone cells. Dideoxy sequencing of the distemper virus PCR products revealed 2% base pair changes in the nucleic acid sequences relative to the Onderstpoort strain of canine distemper. We can conclude that in Paget's disease, canine distemper and possible other paramyxoviruses reside in bone cells and that the persistent nature of the virus may be due to mutations in the viral genome.

Canine distemper virus localised in bone cells of patients with Paget's disease.

The technique of in situ hybridisation was applied using radioactively labelled riboprobes to examine for the presence of canine distemper (CDV) and measles (MV) RNA in Paget's disease of bone. The results indicate that in 41% of Paget's patients, CDV RNA could be detected in osteoclasts, osteoblasts, and osteocytes, but not in controls. In contrast, RNA to the measles virus was not detected. We suggest that CDV may in some cases play a role in the aetiology of Paget's disease.

Bone conditioned medium enhances cell aggregation, cell proliferation and alkaline phosphatase activity in serum-deprived medium.

The effect of medium conditioned by whole bone was examined on the activity of a heterogeneous population of rat calvarial cells grown under serum-deprived conditions. Conditioned medium (CM) had pronounced effects on the appearance of cultures within 24-48 hours of addition. This was characterized by the breakdown of the cell monolayer, rounding of cells and formation of alkaline phosphatase-positive aggregates. Cellular alkaline phosphatase activity was increased compared to controls while acid phosphatase levels were reduced. These aggregates grown in the presence of 10 mM beta-glycerophosphate did not show evidence of mineralization. These results show that soluble factors derived from calvarial bone are responsible for cell aggregation, cell proliferation and increase in alkaline phosphatase activity.

Rapid continuous monitoring of enzyme activity in tissue sections: experience with the M85A and Zeiss UMSP-30 systems.

We have previously described methods for the continuous monitoring of formazan deposition in tissue sections with a system based on the Vickers M85A microdensitometer. However, this instrument only allows the monitoring of a single field in each section. We have now developed a new system based on the Zeiss UMSP-30 microspectrophotometer. This machine is entirely computer controlled and by virtue of its fast-scanning stage allows the rapid (less than 0.5 s) sequential monitoring of multiple fields (up to 35) in each section. Thus a number of cell types may be studied simultaneously and work which used to take a full working day with the M85A system now can be performed in 45 min. As with the M85A the Zeiss system has full capability for data analysis (i.e. calculation of initial velocity rates, etc.). We have found that continuous monitoring of tissue sections by microdensitometry is a precise, sensitive and biochemically valid method of studying enzyme activity within the cellular matrix.

Genetics and biochemical variability of variants of 21 hydroxylase deficiency.

In a population and family study we have examined the relationship between HLA types, classical congenital adrenal hyperplasia (CAH), and variants of 21 hydroxylase (21 OH) deficiency detected by increased blood levels of 17 hydroxyprogesterone (17 PO) in response to ACTH after overnight suppression with dexamethasone ('short Synacthen test'). In a non-CAH population, 7.7% of subjects were found to have raised 17 PO response suggesting reduced activity of 21 OH. Such subjects with raised 17 PO levels were designated simply as type 2 responders because the relationship with genotype was unknown. Post-ACTH levels of 17 PO were significantly greater in type 2 responders than in obligate carriers of CAH. A total of 2.5% of the population studied also had raised progesterone (PO) levels in the Synacthen test. HLA-A28 and B14 (in linkage disequilibrium) were significantly increased in frequency and HLA-B12 decreased in the type 2 responders. HLA-Bw47, which is known to be associated with CAH, was found only among obligate carriers of classical CAH. Because type 2 response and classical CAH are linked to HLA but are associated with different antigens, it is likely that they are determined by two (or more) alleles.

Some characteristics of human adrenal microsomal 21-hydroxylase activity.

The following general characteristics of 21-hydroxylase activity were determined using pooled microsomes obtained from three glands. Enzyme activity exhibited a broad pH dependence, being optimal between pH 7.4-pH 7.8, and was maximal with NADPH in the range 2 to 4.75 X 10(-4)mol/l. No microsomal 21-hydroxylase activity was detected in the absence of NADPH or substrate and when heat denatured microsomes were employed. Enzyme activity was depressed by greater than 75% in the presence of 100% oxygen or nitrogen. In a second set of experiments, microsomal fractions were prepared individually from 7 glands. In the presence of 17 alpha-hydroxy progesterone (2.0 X 10(-7) and 2.0 X 10(-6)mol/l) product formation was linear with time for up to 90 s when the microsomal protein concentration was 5, 10 and 20 micrograms/ml. Between 5 and 30% of the substrate was converted during the first 60 s. In 5/7 of the glands the addition of the autologous cytosol (20 micrograms protein/ml) was without effect, and enzyme activity (using a 60 s reaction and either 2.0 X 10(-7) or 2 X 10(-6)mol/l 17 alpha-hydroxy progesterone was directly proportional to the microsomal protein concentration (range 0-20 micrograms/ml). With the other 2 adrenals 21-hydroxylation was not proportional to the same range of microsomal protein concentrations, although it became so upon the addition of cytosol, which significantly augmented activity. There was considerable variation in enzyme activity between glands from different individuals (Vmax ranging from 2.6 to 16.6 X 10(-9) mol/min/mg protein) and in the apparent Km's (from 0.22 to 1.1 X 10(-6)mol/l). In the two preparations sensitive to cytosol, the Vmax increased 2-fold, and the Km was 3 times lower. Cytosol was without effect upon the kinetic characteristics of the other 5 microsomal preparations. Ascorbic acid (1 X 10(-3) mol/l) depressed enzyme activity by 25-43% whereas oxidised and reduced glutathione (1 X 10(-3) mol/l) showed a slight and variable effect upon 21-hydroxylation.

Prophylactic antibiotic wound irrigation in gastric, biliary, and colonic surgery.

Intermittent intraoperative antibiotic irrigation from the beginning of an operative procedure to its completion is a valuable supplement to hospital and operating room cleanliness and to good surgical technique. A prospective, randomized, double-blind study of 200 patients undergoing clean-contaminated operations on the gastrointestinal tract demonstrated a marked reduction in the incidence of postoperative wound infection and absolute prevention of postoperative peritonitis.

Media and agenda setting: effects on the public, interest group leaders, policy makers, and policy.

Using an experimental design built around a single media event, the authors explored the impact of the media upon the general public, policy makers, interest group leaders, and public policy. The results suggested that the media influenced views about issue importance among the general public and government policy makers. The study suggests, however, that it was not this change in public opinion which led to subsequent policy changes. Instead, policy change resulted from collaboration between journalists and government staff members.