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Biomedical subjects

R Hayward

Publications and source records attributed to R Hayward.

At least 73 records · Page 4Linked to original sources

Integrative vectors for constructing single-copy transcriptional fusions between Bacillus subtilis promoters and various reporter genes encoding heat-stable enzymes.

Here, we report on the construction of three integrative plasmids for Bacillus subtilis (Bs) allowing in vitro construction of transcriptional fusions. These plasmids contain a neomycin- or tetracycline-resistance cassette and one of three promoterless genes: bgaB (encoding beta-galactosidase), cat (chloramphenicol acetyltransferase), or xylE (catechol 2,3-dioxygenase). All cassettes are flanked by the 3'- and 5'-ends of the amyE gene (encoding alpha-amylase) allowing integration of these cassettes at the amyE locus of the Bs chromosome. For propagation and selection in Escherichia coli, the plasmids contain the pBR322 origin of DNA replication and the beta-lactamase-encoding bla gene. Four unique restriction sites can be used for insertion of restriction fragments carrying promoter fragments. All three reporter genes express heat-stable enzymes (stable up to at least 50 degrees C for 30 min) as shown here. We would like to point to the modular nature of these plasmids where the three reporter genes and the two resistance cassettes can be combined in any permutation. The versatility of the promoter-probe vectors was demonstrated by the integration of the promoters of the dnaK and groE operons of Bs and following their heat-inducible expression.

Bacillus subtilis↗

Treatment of obstructive sleep apnoea using nasal CPAP in children with craniofacial dysostoses.

We studied a group of children (aged 2.2-15 years) with craniofacial dysostosis and obstructive sleep apnoea to assess the use of nasal continuous positive airway pressure (n-CPAP) as a palliative form of treatment. A variable period of time was allowed for acclimatisation to n-CPAP (1 day to 2 months), depending on the patient. Patients were then admitted for their first CPAP trial. Baseline breathing difficulty and the effectiveness of n-CPAP were assessed by respiratory sleep studies. Successful results were obtained with n-CPAP in five of the eight patients, with marked clinical and polygraphic improvements of the respiratory pattern immediately after n-CPAP was established. Of the remaining three cases, one child needed a prolonged period of acclimatisation to the n-CPAP system, one was withdrawn from the study, and one failed to respond to n-CPAP and was found to have complete blockage of the upper airways as a result of enlarged adenoids. Our results confirm that n-CPAP can be tolerated even by young patients and can be effective, and that it may be a useful alternative palliative treatment for obstructive sleep apnoea in children with craniofacial syndromes.

Adolescent↗

Removed shunt valves: reasons for failure and implications for valve design.

Most removed shunt valves are discarded with no investigation into why they had to be replaced or whether they still performed to specification. However, improvements in valve design will only occur if valves that have needed removal are examined and the reasons that they failed are determined. An in-depth study of 43 valves that were removed in this unit over a 15-month period was performed. They were submitted to a four-part study, comprising flow-pressure testing, opening and closing pressure measurement, assessment of the susceptibility to syphoning, and dismantling with internal inspection of the valve components. Overall, 81% of valves failed to meet the manufacturers' specified performance data, even though the peroperative cause of shunt failure was thought to lie outside the valve. Over 80% of valves with metallic parts were found to have accumulated debris internally, and this was thought to have impaired their performance. In contrast, only 25% of non-metallic valves contained debris, a significant difference (0.01 > p > 0.001). All of the valves had a high tendency to overdrainage. Attention is drawn to the high number of malfunctioning valves. It is recommended that a change of valve should be considered in all shunt revisions, and that future valve designs should avoid metal components.

Cerebrospinal Fluid Pressure↗

Does the cerebrospinal fluid protein concentration increase the risk of shunt complications?

A prospective study was performed to determine whether the popular opinion that a high CSF protein concentration increases the risk of shunt complications is true. Ninety-five patients were enrolled into the study and they had 116 shunt operations over 15 months. It was considered that the CSF protein content might influence the development of complications that occurred within 2 months of surgery. Shunt complications occurred following 24.6% of operations within this period. This included 12 infections, 13 obstructions and three cases of overdrainage. The distribution of complications, compared to CSF protein content, was non-significant on a chi 2-test (p > 0.5). The total protein content of each of the complication groups was also analysed using the Mann-Whitney U-test and the differences were non-significant for the infection (0.1 > p > 0.05) and obstruction groups (0.5 > p > 0.1). It is concluded that an elevated CSF protein content does not increase the risk of shunt complications, and that there is no reason why shunting should be delayed in patients with a high CSF protein content.

Adolescent↗

The effect of protein and blood cells on the flow-pressure characteristics of shunts.

It has long been assumed that a high cerebrospinal fluid protein concentration adversely affects the performance of shunts. There is little experimental evidence to support this viewpoint, however, and the few reports that have been published can be criticized for poor experimental design or presentation of results. A flow-dependent shunt perfusion model was constructed. PS Medical Flow Control valves (PS Medical Corporation, Goleta, CA) and Cordis-Hakim valves (Cordis Corporates, Miami, FL) were perfused with saline-plasma solutions in concentrations from 0 to 9 g/L of protein. Blood suspensions in dilutions from 0.25 to 1% were also studied. The opening and closing pressures of the valves were measured with a simple manometer, and the physical properties of the solutions were studied. The results indicated that the valves performed within the ranges specified by their manufacturers, even with markedly increased protein concentrations in the perfusate. Furthermore, the valve opening and closing pressures were lower with the protein-containing solutions than with the control solutions. Thus, the protein did not impair shunt function and we conclude that shunts can be inserted into patients who have elevated cerebrospinal fluid protein contents. However, blood cells did adversely affect performance and, therefore, patients with hemorrhagic cerebrospinal fluid should not receive shunts.

Cerebrospinal Fluid Pressure↗

Reduced bacterial adhesion to hydrocephalus shunt catheters mediated by cerebrospinal fluid proteins.

BACKGROUND: Prosthetic infections are a major problem, requiring complex and lengthy management. The role of blood proteins in the pathogenesis of implant infection has been investigated, but research into the role of CSF protein in shunt infections has not been undertaken, even though a high CSF protein has been assumed to increase the risk of such infections. METHODS: New shunt catheters were exposed to either CSF or individual protein solutions, and the numbers of radiolabelled staphylococci that adhered to them were compared with controls that had been exposed to saline only. RESULTS: A significant reduction in bacteria adhering to the test catheter was found in each instance. Furthermore, the CSF with the highest protein content, from a patient with intraventricular haemorrhage, had the greatest inhibitory effect on bacterial adhesion. The effect of the solutions on the hydrophobicity of the silicone rubber was also investigated. The silicone rubber was more hydrophilic, and bacterial adhesion was less, with solutions containing a higher protein content, and these findings were in keeping with the current theories on the mechanism of bacterial adhesion to polymers. CONCLUSIONS: A high CSF protein content does not predispose to the development of shunt infections.

Bacterial Adhesion↗

Spectrum of craniosynostosis phenotypes associated with novel mutations at the fibroblast growth factor receptor 2 locus.

The causative relationship between several of the syndromic forms of craniosynostosis and mutations in the fibroblast growth factor receptor (FGFR) loci is now well established. However, within the group of patients with craniosynostosis, there are several families and sporadic cases whose clinical features differ in variable degrees from the classically described syndromes of craniosynostosis. In this communication we present novel FGFR2 mutations associated with a spectrum of craniosyostosis phenotypes in 4 sporadic cases and in one family in which craniosynostosis segregates. The mutation and phenotype data presented emphasise the clinical variability of mutations at this locus and underline the plasticity of the phenotype-genotype relationship in this important group of congenital malformation syndromes. Mutations found were tyrosine 105 to cysteine, glycine 338 to glutamic acid, serine 351 to cysteine and glycine 384 to arginine. These are the first reported mutations in the first immunoglobulin-like loop (tyrosine 105 to cysteine) and the transmembrane domain (glycine 384 to arginine) of FGFR2, providing further insights into the mechanism of abnormal receptor function in FGFR2 mutations.

Craniosynostoses↗

Managed care and open-heart surgery facilities in California.

More than 25 percent of hospitals in California that offer open-heart surgery performed fewer than the number recommended by minimum volume guidelines in 1991. This DataWatch examines the characteristics of these hospitals and the patients they treat. The analysis suggests that the market share of these providers has remained constant over recent years, despite substantial growth in managed care. Simple explanations--for example, that these hospitals are serving isolated geographic markets or are hospitals in transition--do not explain the phenomenon. Medicare beneficiaries represent approximately half of the patient volume at these facilities. Health maintenance organizations (HMOs) are more likely to send their enrollees to high-volume facilities.

California↗

Subdural intracranial pressure monitoring in craniosynostosis: its role in surgical management.

In the management of craniosynostosis subdural intracranial pressure (ICP) monitoring has proved a useful and safe means of identifying those children with raised ICP who are at risk from its long-term sequelae and who would benefit from early surgical intervention. Overnight subdural ICP recordings have been obtained in 136 unoperated cases of craniosynostosis. Fifteen patients were studied both before and after cranial vault remodelling procedures. ICP was raised (> 15 mmHg) in 35%, borderline (10-15 mmHg) in 37% and normal (< 10 mmHg) in 27% of cases. Raised ICP was present in 28/53 of the syndromic craniofacial dysostosis cases and in 20/83 non-syndromic craniosynostosis cases investigated (P < 0.001). Raised mean ICP and periodic plateaux of sustained ICP during sleep were particularly associated with the syndromic cases. Of the 15 patients studied following cranial vault surgery, 9 showed a reduction in ICP, 3 were unchanged and 3 had higher ICP postoperatively. The results of ICP monitoring can contribute significantly to formulating a rational and staged surgical management plan incorporating the need to normalise ICP and correct the frequently severe functional and cosmetic consequences of these disorders.

Adolescent↗

The adoption of preventive care practice guidelines by primary care physicians: do actions match intentions?

OBJECTIVE: To measure primary care physicians' familiarity with, attitudes toward, and confidence in preventive care practice guidelines for the elderly and to determine whether their attitudes are associated with implementation of guidelines into clinical practice. DESIGN: A self-administered survey of physicians employed by a health maintenance organization (HMO) and of patients cared for by those physicians. Medical records were also reviewed to assess compliance with practice guidelines. SETTING: An HMO in Southern California. PARTICIPANTS: Forty-eight primary care physicians completed the survey (100% response rate). The medical records of 3,249 randomly selected elderly patients (65 to 75 years old) were studied. Of these patients, 2,799 completed a preventive care survey (response rate 86.1%). MEASUREMENT AND RESULTS: Most HMO primary care physicians agreed or strongly agreed that guidelines will improve quality of medical care (88%) and that guidelines have caused them to change their care of patients (73%). Although the physicians' general attitudes about guidelines did not often correlate with their use of preventive care guidelines, the physicians who stated that practice guidelines had changed their practices were more likely to offer their patients clinical breast examinations (75.9% vs 67.2%, p = 0.04) and to counsel their patients to exercise (70% vs 58%, p = 0.01) than were the physicians who did not. There was a significant association between physicians' support for and adoption of specific practice guidelines regarding mammography (r = 0.34, p = 0.02) and immunizations against influenza (r = 0.42, p < 0.005), pneumococcal pneumonia (r = 0.47, p < 0.001), and tetanus (r = 0.31, p = 0.03). CONCLUSIONS: Physicians employed by an HMO were familiar with and hopeful about the role of guidelines for improving patient care. Physicians' attitudes toward specific preventive care guidelines and admission that guidelines had caused them to change their practice did at times, but not always, correlate with their implementation of guidelines into clinical practice.

Adult↗

Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes.

Mutations in the fibroblast growth factor receptor 2 (FGFR2) gene have been identified in Crouzon syndrome, an autosomal dominant condition causing premature fusion of the cranial sutures (craniosynostosis). A mutation in FGFR1 has been established in several families with Pfeiffer syndrome, where craniosynostosis is associated with specific digital abnormalities. We now report point mutations in FGFR2 in seven sporadic Pfeiffer syndrome patients. Six of the seven Pfeiffer syndrome patients share two missense mutations, which have also been reported in Crouzon syndrome. The Crouzon and Pfeiffer phenotypes usually breed true within families and the finding of identical mutations in unrelated individuals giving different phenotypes is a highly unexpected observation.

Acrocephalosyndactylia↗

Physical properties of cerebrospinal fluid of relevance to shunt function. 1: The effect of protein upon CSF viscosity.

Viscosity is the resistance to flow of a fluid and it is the only property of a fluid that will affect its flow through a system of valveless tubing (surface tension will affect the opening and closing of valves that are included in the system). The effect that an elevated protein concentration has upon CSF viscosity has received little study, yet many neurosurgeons believe that CSF with an elevated protein content is too viscous to flow satisfactorily through shunts. The total protein content and viscosity of 126 specimens of CSF from hydrocephalic patients were measured and analysed with reference to the aetiology of the hydrocephalus. The results indicate that high protein concentrations do not greatly affect the viscosity of CSF, and that the aetiology is also of little consequence. These findings were highly significant on linear regression analysis (p < 0.001). The flow of the most viscous CSF that is likely to be encountered would be reduced by only 7% through a given catheter, compared with that of the least viscous CSF.

Adolescent↗

Physical properties of cerebrospinal fluid of relevance to shunt function. 2: The effect of protein upon CSF surface tension and contact angle.

CSF surface tension has received little study, and yet it will effect the pressure at which shunt valves operate, and by influencing the degree of hydrophobicity (contact angle) will alter the attraction between bacteria and neurosurgical prostheses. A study is therefore presented of the effect of protein content upon the surface tension of CSF and its contact angle to silicone rubber. Both of these quantities fell throughout the normal range of CSF protein, but above 1 g/l, additional protein had little effect, and the results obtained were similar to that reported for plasma. The effect of surface tension on the opening and closing pressures of hydrocephalus shunt valves and of contact angle in the adhesion of bacteria to neurosurgical implants is discussed.

Adolescent↗

New autosomal dominant form of spondyloepiphyseal dysplasia presenting with atlanto-axial instability.

We present a family with a radiologically distinct new form of autosomal dominant spondyloepiphyseal dysplasia, presenting with cervical instability and attendant neurological compromise and emphasise the radiological characteristics which delineate this condition. Cervical vertebral abnormalities, including malformation of the odontoid process, have been observed in some forms of spondyloepiphyseal dysplasia, but rarely lead to neurological sequelae, in contrast to the pedigree we describe.

Atlanto-Axial Joint↗