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Biomedical subjects

J Phillips

Publications and source records attributed to J Phillips.

At least 19 recordsLinked to original sources

Third-generation cephalosporin resistance among Gram-negative bacilli causing meningitis in neurosurgical patients: significant challenges in ensuring effective antibiotic therapy.

OBJECTIVES: The treatment of meningitis caused by Gram-negative bacilli in neurosurgical patients is a major challenge because of the complexity of these patients, the emergence of antibiotic resistance in many of the causative organisms and the restricted choice of antibiotics suitable for use, owing to a failure to achieve high enough concentrations in the CSF. We reviewed the incidence, aetiology, treatment and outcome of all patients with Gram-negative bacillary meningitis (GNBM) in our centre over a 7 year period. METHODS: Beaumont Hospital, Dublin is a 720 bed tertiary referral hospital and contains the national neurosurgical centre for the Republic of Ireland. The case notes and microbiological records of all patients with GNBM between 1998 and 2004 inclusive were reviewed retrospectively. Only patients with positive CSF culture and clinical features compatible with meningitis were included. RESULTS: Forty separate episodes of GNBM involving 34 different patients occurred during the study period. The most common causative organisms were Enterobacter spp. (35%), Escherichia coli (22.5%) and Pseudomonas aeruginosa (15%). Twenty-five per cent of isolates were resistant to third-generation cephalosporins. The median duration of treatment was 19.2 days and a combination of intravenous and intraventricular antibiotics was the most common treatment regimen used. Mortality directly related to GNBM was 2.5%. CONCLUSIONS: Although the mortality directly related to GNBM was low, the emergence of strains resistant to third-generation cephalosporins represents a therapeutic challenge. Treatment with combined intravenous and intraventricular antibiotics is recommended for 2-3 weeks, but more studies are required to determine the optimal management of this difficult condition.

Adult↗

Acceptability of routine antenatal psychosocial assessments to women from English and non-English speaking backgrounds.

The acceptability of routine psychosocial assessments to women and staff at an antenatal clinic of a public hospital in Sydney, Australia, was investigated. 104 English-speaking women had a telephone interview within a few days of the psychosocial assessment, and 65 of these women also participated in a telephone interview 5-8 weeks after the birth. 14 midwives who had administered the questions were also interviewed. These three sets of interviews indicated that the majority of women and staff considered the psychosocial questions to be appropriate and helpful. Prior to introducing a shorter version of the psychosocial assessment for all women, consultations took place with health professionals and community women from Arabic-speaking (n = 30) and Vietnamese-speaking (n = 39) backgrounds to determine the expected suitability of such questions to women from these ethnic backgrounds. The only consistent concern was that the term 'husband' should replace 'partner' when interviewing Arabic-speaking women. Telephone interviews were then conducted with a sample of Arabic-speaking (n = 48) and Vietnamese-speaking (n = 50) women within a few days after they had been to the clinic. As with the English-speaking women, most considered the questions to be appropriate and acceptable.

Cultural Diversity↗

The effects of ligand chain length, salt concentration and temperature on the adsorption of bovine serum albumin onto polypropyleneglycol-Sepharose.

The interaction thermodynamics associated with bovine serum albumin adsorption on polypropylene glycol (n=3)-Sepharose CL-6B and polypropylene glycol (n=7)-Sepharose CL-6B, using ammonium sulfate as the modulator was studied. Analysis of data under linear conditions was accomplished with the stoichiometric displacement retention model, preferential interaction approach and van't Hoff plots applied to HIC systems. Preferential interaction analysis indicated a strong entropic driving force under linear conditions, due to the release of a large amount of solvent on adsorption. In contrast, flow microcalorimetry under overloaded conditions showed that the adsorption of bovine serum albumin may be entropically or enthalpically driven. It is postulated that adsorption in the nonlinear region is influenced by the degree of water release, protein-protein interactions on the surface, reorientation of ligand, and conformational changes in the protein.

Adsorption↗

Effects of miglyol 812 on rats after 4 weeks of gavage as compared with methylcellulose/tween 80.

Miglyol 812 is a medium-chain triglyceride used in toxicology studies as an excipient to improve test compound solubility/absorption. As part of a larger toxicology study, 15 Wistar Han IGS rats/sex/group were dosed by oral gavage for 4 weeks with 10 mL kg(-1) day(-1) of 100% Miglyol 812 or 0.5% methylcellulose/0.1% Tween 80 in water (MC-T) followed by 4 weeks without treatment to evaluate the potential effects of this excipient in long-term toxicology studies relative to a traditional excipient such as MC-T. Clinical signs evident during the dosing phase included soft and/or mucoid stool in 12/15 males and 11/15 females treated with Miglyol 812 but in no animals treated with MC-T. Animals treated with Miglyol 812 had a 6-7% statistically significant reduction in body weight gain as compared to MC-T-treated animals. Statistically significant changes in clinical chemistry parameters as compared to MC-T included decreased blood urea nitrogen (50% and 29% in males and females, respectively), increased cholesterol (1.6-fold and 1.5-fold in males and females, respectively), decreased total protein (6% and 8% in males and females, respectively), decreased globulins (15% and 11% in males and females, respectively), and increased triglycerides (2.8-fold and 1.7-fold in males and females, respectively). Absolute and relative thymic weights decreased 28% and 24%, respectively, in males, and 18% and 17%, respectively, in females without histological alterations. Histopathology revealed increased alveolar histiocytosis with focal interstitial inflammation in lungs in 5/10 males and 7/10 females treated with Miglyol 812 compared to only 1/10 males and 1/10 females treated with MC-T. All effects were reversible during the recovery period. Results of this study indicate that 100% miglyol 812 produces reversible gastrointestinal effects and decreases in body weight gains along with changes in several serum chemistry parameters. Therefore, it should not be considered innocuous when delivered by oral gavage in long-term rodent toxicology studies.

Animals↗

Assessment of anger coping skills in individuals with intellectual disabilities.

Recent controlled studies have supported the effectiveness of anger management training for people with intellectual disabilities (IDs). This report describes an evaluation instrument designed to assess their usage of specific anger coping skills. The Profile of Anger Coping Skills (PACS) is designed for completion by a staff member or carer. Three situations are first elicited in which a client frequently displays anger. The respondent then rates each situation for the extent to which the client deploys each of eight behavioural and cognitive coping skills. In a preliminary reliability study, 20 users of a day service for people with IDs were rated independently by two staff members, with one of them completing the assessment on two separate occasions: the PACS showed good test-retest reliability and lower, but still acceptable, interrater reliability. The PACS was subsequently used, in a different day service, as part of the assessment pack administered before and after a 12-week anger management group, with a parallel assessment of an untreated control group. The treated group showed substantial decreases in measures of anger, which were maintained at 6-month follow-up. Increases in PACS-rated anger coping skills were also seen in all participants in the anger management group, but not in the control group. There were differences in the extent to which different coping skills were acquired by the treated group, and there were also individual differences in the profile of specific skills acquired. It is concluded that the PACS is a reliable instrument for assessing anger coping skills, particularly when used repeatedly with the same informant. It provides information that is useful for both individual care planning and the design of future anger management programmes.

Adaptation, Psychological↗

The laparoscopic nephrectomy learning curve: a single centre's development of a de novo practice.

OBJECTIVE: There has been a dramatic increase in the interest and practice of laparoscopic urology, with nephrectomy having become the commonest laparoscopic urological procedure. Compared with open nephrectomy, it results in reduced morbidity and shorter convalescence times while maintaining oncological safety. However, while these results predominately stem from institutions with well developed laparoscopic programmes, little is known about the results in centres that have newly adopted this technique. The introduction of a laparoscopic urological service at the Royal Hallamshire Hospital provided an opportunity to study these factors. METHODS: Since the appointment in October 2000 of a urological surgeon (N Oakley) to develop the laparoscopic service, there have been over 200 laparoscopic procedures including 121 nephrectomies performed at this centre. Full details were collected for each of these cases, and in addition, compared with retrospective data for 50 open nephrectomies performed during the same time period. RESULTS: With increased operator experience the median operative duration, complication, transfusion, and conversion rates significantly improved. While a learning curve was evident, the overall operative complication (9%) and conversion rates (6%) were low, in addition to patient morbidity (16.5%) and mortality (0%) rates, showing that this learning curve had no deleterious effects upon patient care. The median hospital stay was four days, which reduced to three with experience and was significantly shorter than for open nephrectomy at this institution (p = 0.001). CONCLUSIONS: The development of a successful laparoscopic programme can be achieved with a comparatively short learning curve and without detriment to the patient provided the necessary steps are observed.

Carcinoma, Renal Cell↗

Routine psychosocial assessment of women in the antenatal period: frequency of risk factors and implications for clinical services.

Routine psychosocial assessment was introduced at an Australian public hospital's antenatal clinic in 2001. After modification, this assessment consists of 12 questions together with the Edinburgh Depression Scale (EDS). Data are reported for responses to these questions from over 2,000 English-speaking women presenting to the clinic in a 12-month period. These 12 questions and the EDS were categorised into seven risk domains, with 12% of the women (n = 260) having three or more of these risk domains. Referral information to one of our two clinical services shows that 6.7% of women assessed in the antenatal clinic become clients having face-face counselling, and a further 7.2% have just telephone contact with this specialist perinatal mental health service. This information should prove useful for services considering implementing routine psychosocial assessments (or "screening") in the antenatal period.

Adult↗

The neural areas that control the retrieval and selection of semantics.

Semantic retrieval consistently activates left inferior frontal regions, yet lesions to these areas do not typically result in semantic deficits. This discrepancy has led to the hypothesis that left prefrontal areas are primarily involved in executive processes while semantic information is retrieved from temporal cortices. We investigated semantic executive processing by changing, over trials, the semantic association to a stimulus. Using fMRI and PET, we demonstrate that changes in semantic association increased activation in temporal as well as frontal areas. The similar effects in temporal and frontal areas suggest that semantic executive processes are not confined to the left inferior frontal cortex but might be distributed throughout the semantic system.

Adult↗

Abnormal regulation of thirst and vasopressin secretion following surgery for craniopharyngioma.

OBJECTIVE: In this study we aimed to establish the frequency of postoperative diabetes insipidus and the incidence and characteristics of abnormalities of thirst in a cohort of patients with craniopharyngioma, in whom neurosurgery had been performed. DESIGN: Diabetes insipidus was determined by either standard criteria for diagnosis in the immediate postoperative period, or by water deprivation test, in all craniopharyngioma and pituitary tumour patients who underwent surgery in Beaumont Hospital between the years 1986 and 1998. Osmoregulated thirst and vasopressin release were studied during a 2-h infusion of hypertonic (5%) saline followed by a 30-min period of free access to water. PATIENTS: Data on the incidence of postoperative diabetes insipidus was collected in 26 patients with craniopharyngioma and 154 patients with pituitary adenomata. We recruited 16 healthy control patients, 16 patients with cranial diabetes insipidus following pituitary tumour surgery and 16 patients with cranial diabetes insipidus following craniopharyngioma resection for the hypertonic saline infusion study. RESULTS: Twenty-five patients out of 26 (96%) patients developed diabetes insipidus after surgery for craniopharyngioma, a much higher incidence than after surgery for suprasellar (26/88, 30%, P < 0.001) or intrasellar pituitary tumours (9/66, 14%, P < 0.001). Hypertonic saline infusion identified abnormal thirst responses in five of the 16 craniopharygioma patients studied; all of the pituitary tumour patients had a normal thirst response. Three of the craniopharyngioma patients had adipsic diabetes insipidus whilst two had polydipsic diabetes insipidus. CONCLUSION: This study demonstrates following surgery for craniopharyngioma there is a high incidence of cranial diabetes insipidus and a significant incidence of abnormal thirst responses to osmotic stimuli.

Adult↗

Management of acute cholecystitis in UK hospitals: time for a change.

Early cholecystectomy for patients with acute cholecystitis is safe, cost effective, and leads to less time off work compared with delayed surgery. This study was designed to assess current practice in the management of acute cholecystitis in the UK. A postal questionnaire was sent to 440 consultant general surgeons to ascertain their current management of patients with acute cholecystitis. Replies were received from 308 consultants who were involved in treating patients with acute cholecystitis of whom 18 transferred these patients on to another team for further management the day after admission. Thirty two consultants (11%) routinely treated patients by early cholecystectomy, with limiting factors stated to be the availability of surgical staff, theatre space, and radiological investigations. The remaining consultants (n = 258) routinely manage their patients conservatively with intravenous antibiotics and allow the inflammation to resolve before undertaking cholecystectomy at a later date. Indications for undertaking early cholecystectomy during the first admission by this latter group included the presence of spreading peritonitis due to bile leak, empyema, and unexpected space on theatre list. The commonest method for both elective and early cholecystectomy is laparoscopic, but the percentage of consultants using an open method rises from 8% in the elective situation to 47% for urgent early cholecystectomy. Despite evidence which strongly advocates early cholecystectomy, this practice is routinely carried out by only 11% of consultants in the UK at present.

Acute Disease↗

Autologous free tissue breast reconstruction using the internal mammary perforators as recipient vessels.

Perforator flaps have become popular for autologous free tissue breast reconstruction because they reduce the donor site morbidity. It is possible to apply the this principle to the recipient site. We present our experience of using the perforating vessels from the internal mammary artery and vein as recipient vessels for autologous free tissue breast reconstruction flaps in 21 out of 54 consecutive cases (39%). We discuss the technique and its advantages.

Anastomosis, Surgical↗

A twelve-year review of central nervous system bacterial abscesses; presentation and aetiology.

OBJECTIVES: To review and document the changing patterns in diagnosis, causes and treatment of bacterial infections of the central nervous system (CNS) in a national neurosurgical unit only in patients from whom a specimen was obtained for culture. METHODS: The case notes, radiological results and laboratory records of all 163 patients in our institution who underwent a neurosurgical procedure between 1988 and 2000 for a CNS abscess in a national center were reviewed retrospectively. Those patients from whom there were no operative specimens (i.e. neurosurgical intervention was not performed) and who were treated empirically were excluded, as were patients with mycobacterial infection. RESULTS: The mean age of the 163 patients was 35.2 years. Headache, pyrexia and an altered mental state were the commonest presentations. The frontal lobe was the commonest anatomical site (62 patients, 38%) and the majority of abscesses occurred following community infections such as sinusitis and mastoiditis; no primary source could be identified in 32 (20%) patients. Bacteria were isolated from 73% of patients and polymicrobial infections occurred in 29 (17.7%) patients. Anaerobes accounted for only 13.6% of isolates and methicillin-resistant Staphylococcus aureus (MRSA) was isolated on five occasions, all in the last five years of this review. Sixteen (9.8%) patients died prior to discharge or transfer back to the original referring hospital and 18 (11%) patients developed epilepsy. CONCLUSION: There was a relatively high incidence of polymicrobial infection but the number of specimens with anaerobes was small, which may be because of the use of empiric metronidazole before surgical intervention. Most infections were community-acquired and responded well to a combination of surgical drainage and antibiotic therapy. The emergence of MRSA in this group of patients is, however, worrying.

Adolescent↗

Effect of nitrous oxide on intracellular events of GT1-7 GnRH-secreting neurons.

Exposure to nitrous oxide (N2O) may result in decreased fertility and other reproductive problems in women working in dental offices. This study explored direct effects of N2O on gonadotropin-releasing hormone (GnRH) neurons involved in pituitary-gonadal function. An immortalized GnRH-secreting GT1-7 cell line was used to evaluate the effects of 60% N2O exposure for 24 hours on pro-GnRH mRNA levels, KCl-stimulated GnRH levels, and certain signaling pathways. N2O exposure for 24 hours decreased pro-GnRH mRNA levels by approximately 80% without affecting cell viability or intracellular GnRH levels. The ability of KCl to release GnRH stores was also significantly reduced. Western blot analyses of ERK1/2, and p38 phosphorylation and IkappaB did not indicate any change in phosphorylation, although p63 tyrosine phosphorylation was increased after short-term N2O exposure. Levels of c-fos, a nuclear transcription factor, were not changed by N2O exposure. These results indicate that N2O significantly decreases evoked release of GnRH as well as GnRH mRNA levels either by decreased synthesis or by mRNA stability. These results may be important in understanding adverse effects of N2O on female workers in dental practice where the gas is not scavenged.

Analysis of Variance↗

Mouse models of human cancer web-based resources.

The Mouse Models of Human Cancers Consortium (MMHCC) is a collaborative program designed to derive and characterize mouse models of human malignancies. To enhance information and resource exchange among the MMHCC investigators and other cancer research scientists, the NCI Center for Bioinformatics (NCICB, http://ncicb.nci.nih.gov/) has developed web-based resources that are freely available to the cancer research community. These resources include a website (http://emice.nci.nih.gov) and databases for cancer models (http://cancermodels.nci.nih.gov) and cancer images (http://cancerimages.nci.nih.gov).

Animals↗

Baroregulation of vasopressin release in adipsic diabetes insipidus.

Adipsic diabetes insipidus (ADI) occurs in association with a heterogeneous group of conditions. We report vasopressin (AVP) responses to hypotension in nine patients with ADI and nine controls. Hypertonic saline infusion produced absent thirst (1.7 +/- 1.7 to 1.5 +/- 1.7 cm, P = 0.99) and AVP responses (0.3 +/- 0.1 to 0.4 +/- 0.1 pmol/liter, P = 0.99) in the ADI group, who also drank less than the control group (258 +/- 200 ml vs. 1544 +/- 306 ml, P < 0.001). Intravenous infusion of trimetaphan camsylate produced a fall in mean arterial pressure of 31.6% +/- 8.9% in patients and 29.4% +/- 6.1% in controls. Plasma AVP concentrations rose from 1.4 +/- 0.8 to 340.3 +/- 497.4 pmol/liter (P < 0.001) in the control group. In three patients with craniopharyngioma, there was no rise in plasma AVP concentrations (0.3 +/- 0.1 to 0.3 +/- 0.1 pmol/liter, P = 0.96), but plasma AVP rose significantly in response to hypotension in the other six patients (0.4 +/- 0.2 to 204.5 +/- 223.2 pmol/liter, P < 0.001). We concluded that the AVP responses to hypotension in ADI are heterogeneous and reflect the site of the lesion causing the diabetes insipidus.

Adolescent↗