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Biomedical subjects

C Fowler

Publications and source records attributed to C Fowler.

At least 19 recordsLinked to original sources
PubMed2006

Symposium report on urothelial dysfunction: pathophysiology and novel therapies.

PURPOSE: The basic premise of this symposium (Workshop 7) at the 2004 International Continence Society meeting in Paris was to elucidate different mechanisms of urothelial cell pathology, explore their impact on bladder function and discuss novel therapeutic interventions. RESULTS: The topics included 1) urothelial structure and function, 2) the role of adenosine triphosphate in urothelial signaling and cystitis, 3) lamina propria myofibroblasts and purinergic receptors, 4) antiproliferative factor involvement in interstitial cystitis, 5) the urothelium as a reservoir for bacterial infections, 6) radiation cystitis, nitric oxide and gene therapy, and 7) intravesical treatments. DISCUSSION: It was agreed that the urothelium can no longer be regarded merely as a passive barrier separating urine from the underlying tissues. The epithelial cells of the urothelium form part of an integrated network that also includes afferent and possibly efferent nerves, and suburothelial myofibroblasts. It has a central role in several functions, including bladder wall sensation, local blood flow modulation, pathogen removal and active barrier provision. These functions are achieved through several autocrine and paracrine pathways that involve transmitter release from the urothelium and its ability to integrate incoming signals through its battery of membrane receptors. Several pathological processes were discussed using this knowledge, including the role of small glycoproteins released during interstitial cystitis, the molecular basis of radiation induced urothelial damage, the origin of recurrent urinary tract infections and the mode of action of potential intravesical treatments for overactive bladder. CONCLUSIONS: Overall it was concluded that the urothelium has a key role in regulating lower urinary tract physiology and pathology.

Animals↗
PubMed2005

The European Multiple System Atrophy-Study Group (EMSA-SG).

Introduction. The European Multiple System Atrophy-Study Group (EMSA-SG) is an academic network comprising 23 centers across Europe and Israel that has constituted itself already in January 1999. This international forum of established experts under the guidance of the University Hospital of Innsbruck as coordinating center is supported by the 5th framework program of the European Union since March 2001 (QLK6-CT-2000-00661). Objectives. Primary goals of the network include (1) a central Registry for European multiple system atrophy (MSA) patients, (2) a decentralized DNA Bank, (3) the development and validation of the novel Unified MSA Rating Scale (UMSARS), (4) the conduction of a Natural History Study (NHS), and (5) the planning or implementation of interventional therapeutic trials. Methods. The EMSA-SG Registry is a computerized data bank localized at the coordinating centre in Innsbruck collecting diagnostic and therapeutic data of MSA patients. Blood samples of patients and controls are recruited into the DNA Bank. The UMSARS is a novel specific rating instrument that has been developed and validated by the EMSA-SG. The NHS comprises assessments of basic anthropometric data as well as a range of scales including the UMSARS, Unified Parkinson's Disease Rating Scale (UPDRS), measures of global disability, Red Flag list, MMSE (Mini Mental State Examination), quality of live measures, i.e. EuroQoL 5D (EQ-5D) and Medical Outcome Study Short Form (SF-36) as well as the Beck Depression Inventory (BDI). In a subgroup of patients dysautonomic features are recorded in detail using the Queen Square Cardiovascular Autonomic Function Test Battery, the Composite Autonomic Symptom Scale (COMPASS) and measurements of residual urinary volume. Most of these measures are repeated at 6-monthly follow up visits for a total study period of 24 months. Surrogate markers of the disease progression are identified by the EMSA-SG using magnetic resonance and diffusion weighted imaging (MRI and DWI, respectively). Results. 412 patients have been recruited into the Registry so far. Probable MSA-P was the most common diagnosis (49% of cases). 507 patients donated DNA for research. 131 patients have been recruited into the NHS. There was a rapid deterioration of the motor disorder (in particular akinesia) by 26.1% of the UMSARS II, and - to a lesser degree - of activities of daily living by 16.8% of the UMSARS I in relation to the respective baseline scores. Motor progression was associated with low motor or global disability as well as low akinesia or cerebellar subscores at baseline. Mental function did not deteriorate during this short follow up period. Conclusion. For the first time, prospective data concerning disease progression are available. Such data about the natural history and prognosis of MSA as well as surrogate markers of disease process allow planning and implementation of multi-centre phase II/III neuroprotective intervention trials within the next years more effectively. Indeed, a trial on growth hormone in MSA has just been completed, and another on minocycline will be completed by the end of this year.

Animals↗
PubMed2005

Randomised evaluation of alternative electrosurgical modalities to treat bladder outflow obstruction in men with benign prostatic hyperplasia.

OBJECTIVES: To compare and evaluate the clinical and cost-effectiveness of transurethral vaporisation of the prostate (TUVP), a new electrosurgical modality, with the standard treatment, transurethral resection of the prostate (TURP). DESIGN: A multicentre randomised controlled trial of pragmatic design with associated economic evaluation using cost minimisation. SETTING: Patients were recruited from four centres in south-east England. PARTICIPANTS: Men requiring surgery for lower urinary tract symptoms deemed to be due to benign prostatic hypertrophy. INTERVENTIONS: TURP was performed and subsequent management conducted according to the usual practice of the clinical team. TUVP was performed with the most promising available equipment using a technique described in the literature. Postoperative management after TUVP was left to the ward team, who were not necessarily informed to which treatment arm the patient had been allocated. For the purpose of the study, patients were assessed clinically, by questionnaire and investigation at baseline, 2 months and 6 months after randomisation. A long-term follow-up postal questionnaire was sent to each patient at 2 years. For the economic evaluation, direct costs from the NHS viewpoint were collected. MAIN OUTCOME MEASURES: A reduction of at least 5 from the International Prostate Symptom Score (IPSS) was taken as a satisfactory outcome. The IPSS quality of life (QoL) question provided disease-specific information about QoL. Secondary outcome measures included urinary flow rate, post-void urinary volume, prostate volume and pressure-flow urodynamics. Questionnaires used included SF-36, EuroQol and a sexual function section based on the International Continence Society 'Benign Prostatic Hyperplasia' (ICS-BPH) questionnaire. Measurement of full blood count and urea and electrolytes was made at baseline and at 24 hours. Adverse events were recorded during the hospital stay and at follow-up visits. RESULTS: TURP and TUVP were both effective in producing a clinically important reduction in IPSS and positive change in the IPSS QoL question. The success rate for relief of symptoms was 85% for TURP and 74% for TUVP. Neither the success of the treatment nor the change in aggregated IPSS was significantly different between the groups. The improvement was sustained to 24 months after treatment with no significant difference between the groups. The effectiveness of both treatments was also equivalent when assessed through improvement in objective measures of urinary tract function, reduction in prostate size and the change in health questions of SF-36. The absolute incidence of adverse events was similar between the two groups. The incidence of severe or prolonged bleeding was less with TUVP, as evidenced by the need for blood transfusion and the drop in haemoglobin level 24 hours postoperatively. TURP and TUVP are broadly equivalent in direct NHS resource use. This study did not show any significant difference in inpatient stay or use of outpatient resources between the groups. The disposable electrodes used for TUVP are more expensive than reusable TURP electrodes. CONCLUSIONS: TURP and TUVP are equivalently effective in improving the symptoms of benign prostatic enlargement over at least 2 years. TUVP is associated with less morbidity due to haemorrhage than TURP. Replacement of TURP by TUVP would not produce a significant cost benefit to the NHS unless a reduction hospital inpatient stay of at least 1 day could be secured. Further research is necessary to determine why patients stay in hospital after transurethral surgery to the prostate and how a reduction in the length of stay can be achieved. A much larger observational study/audit is required to assess the incidence of infrequently occurring adverse events after TUVP. Longer term follow-up is also needed.

Aged↗
PubMed2002

Penetration of levofloxacin into skin tissue after oral administration of multiple 750 mg once-daily doses.

OBJECTIVE: To probe the pharmacokinetic basis for the use of levofloxacin for complicated skin and skin-structure infections (SSSIs) at a once-daily dosage of 750 mg by investigating its penetration into skin tissue. METHOD: Ten healthy volunteers were administered three oral, once-daily 750 mg doses of levofloxacin, and levofloxacin concentrations were subsequently measured over time (0.5-24 h) in skin-punch biopsy tissue and plasma. RESULTS: Skin tissue concentrations consistently exceeded those in plasma at every time point, with tissue/plasma ratios of 1.37 +/- 0.81 for peak concentration and 1.97 +/- 0.35 for area under the concentration versus time curve. Three of the ten subjects reported treatment-emergent adverse events (AEs) that were considered unrelated to treatment. An 11th subject who had enrolled in the study withdrew after AEs of mild severity that were possibly related to the study drug. CONCLUSION: The results support the clinical usage of levofloxacin 750 mg once-daily for complicated SSSIs.

Administration, Oral↗
PubMed2001

RWJ-270201 (BCX-1812): a novel neuraminidase inhibitor for influenza.

The influenza virus neuraminidase (NA) is important in the pathogenesis of infection and, thus, is an attractive target for agents used in the treatment and prophylaxis of influenza. This article describes preclinical and early clinical data related to RWJ-270201 (BCX-1812), a novel, orally active NA inhibitor that was rationally designed for having potent and selective activity against influenza A and B viruses. RWJ-270201 is a unique NA inhibitor with a cyclopentane ring structure and high selectivity for the influenza NA. RWJ-270201 has efficacy comparable to or better than earlier NA inhibitors against a wide range of influenza A and B isolates, including recently emerged and avian strains, both in vitro and in a lethal murine model of influenza. Based on the high selectivity and efficacy of RWJ-270201 against both type A and B influenza strains in preclinical studies as well as murine pharmacodynamic studies supporting the potential for once-daily administration, clinical trials were initiated in order to determine the tolerability and antiviral activity of RWJ-270201 in humans. To date, clinical studies have indicated that RWJ-270201 is well tolerated and has antiviral activity in human experimental influenza models when administered orally once daily.

Acids, Carbocyclic↗
PubMed2001

Selective spinal anesthesia for outpatient laparoscopy. III: sufentanil vs lidocaine-sufentanil.

PURPOSE: The efficacy of low dose intrathecal lidocaine-sufentanil was compared with intrathecal sufentanil for short duration outpatient gynecological laparoscopy. METHODS: Thirteen ASA I and II patients undergoing gynecological laparoscopy were studied in a randomized double-blind trial. Patients received either intrathecal 10 mg lidocaine plus 10 microg sufentanil (Group LS) or intrathecal 20 microg sufentanil (Group S), each diluted to 3 mL with sterile water through a 27g Whitacre needle in the sitting position. Sensory and motor recovery were assessed with pinprick and a modified Bromage scale. RESULTS: One of seven Group LS patients and two of five Group S patients required conversion to general anesthesia for failed skin test with forceps. Two of the remaining three Group S patients felt sharpness with skin incision. The study was terminated early because of inadequate anesthesia in Group S. The small sample size (n = 9) made statistical analysis uninformative. CONCLUSION: Intrathecal 20 microg sufentanil is unsuitable as a sole agent for gynecological laparoscopy.

Adult↗
PubMed2001

Preventing and managing exercise-induced asthma.

Managing exercise-induced asthma is a challenge for the patient and the clinician. As the incidence of exercise-induced asthma increases, health care providers need effective protocols to diagnose and treat these patients in outpatient settings. This article discusses the incidence, risk factors, pathophysiology, diagnosis, and treatment of exercise-induced asthma. Both traditional and new methods of disease diagnosis and treatment in the outpatient setting are explored.

Adult↗
PubMed2001

Long-term physical impairment and functional outcomes after complex facial fractures.

To develop an understanding of the expected functional outcomes after facial trauma, a retrospective cohort study of patients with complex facial fractures was conducted. A cohort of adults aged 18 to 55 years who were admitted to the R. Adams Cowley Shock Trauma Center between July of 1986 and July of 1994 for treatment of a Le Fort midface fracture (resulting from blunt force) was retrospectively identified. Outcomes of interest included measures of general health status and psychosocial well being in addition to self-reported somatic symptoms. General health status was ascertained using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). The Body Satisfaction Scale was used to define patient concerns about altered body image and shape. To determine whether complex maxillofacial trauma and facial fractures contributed to altered social interactions, the Social Avoidance and Distress scale was used. In addition, information about a patient, his or her injury, and its treatment were ascertained from the medical records. Using the methods described above, 265 patients with Le Fort fractures were identified. These individuals were matched to a similar group of 242 general injury patients. A total of 190 of the Le Fort patients (72 percent of those eligible for the study) and 144 (60 percent) general injury patients were successfully located, and long-term interview data were acquired.Le Fort fracture patients as a group had similar health status outcomes when compared with the group of general injury patients. However, when outcomes were examined by the complexity of the Le Fort fracture, the authors found that study subjects with severe, comminuted Le Fort injuries (group D) had significantly lower SF-36 scores (worse outcomes) for the two dimensions related to role limitations: role limitations due to physical problems and role limitations due to emotional problems (p < 0.05). SF-36 scores for all other dimensions except physical function were also lower for comminuted versus less complex Le Fort fractures, although differences were not statistically significant.Specifically, there was a direct relationship between severity of facial injury and patients reporting work disability. Of group C and D Le Fort patients (severely comminuted fractures) only 55 and 58 percent, respectively, had returned to work at the time of follow-up interview. These figures are significantly lower than the back-to-work percentage of patients with less severe facial injury (70 percent). When study participants were asked if they were experiencing specific somatic symptoms at the time of the interview that they had not experienced before the injury, a significantly larger percent of the Le Fort fracture patients (compared with the general injury patients) responded in the affirmative. Differences between the Le Fort fracture and general injury groups were statistically significant (p < 0.05) for all 11 symptoms. The percentage of patients reporting complaints increased with increasing complexity of facial fracture in the areas of visual problems, alterations in smell, difficulty with mastication, difficulty with breathing, and epiphora, and these differences reached statistical significance. Patients sustaining comminuted Le Fort facial fractures report poorer health outcomes than patients with less severe facial injury and substantially worse outcomes than population norms. It is also this severely injured population that reports the greatest percentage of injury-related disability, preventing employment at long-term follow-up. The long-term goal of centralized tertiary trauma treatment centers must be to return the patient to a productive, active lifestyle.

Activities of Daily Living↗
PubMed2001

Safety and pharmacokinetics of multiple 750-milligram doses of intravenous levofloxacin in healthy volunteers.

The safety and pharmacokinetics of a once-daily high intravenous dose of levofloxacin (750 mg) in 18 healthy volunteers were studied in a double-blind, randomized, placebo-controlled, single-center parallel group study. Levofloxacin was well tolerated, and higher maximum concentration of drug in serum and area under the concentration-time curve values were achieved. For difficult-to-treat infections, high daily doses of levofloxacin may be beneficial, and intravenous administration may be preferred in certain clinical settings, such as when treating patients in intensive care units, warranting further evaluation.

Adult↗
PubMed2000

International Narcotics Research--31st Conference.

This well-rounded meeting brought together scientists from behavioral, molecular and synthetic fields of opioid research. Highlights for this meeting included the genetics of opioid abuse, the use of cDNA microarrays to identify gene expression in response to opiates, how pain can modulate opioid tolerance, and the role of cholecystokinin (CCK) in associative morphine tolerance. Other excellent sessions included discussions on the use of opiates for the treatment of drug abuse, and poster presentations discussing novel opiates for the treatment of inflammatory pain.

Journal Article↗
PubMed1999

Can nurses screen all outpatients? Performance of a nurse based model.

PURPOSE: This paper outlines and evaluates a nurse based model for screening outpatients that is utilized in our free standing Surgical Day Care Centre (SDCC). METHODS: For 668 outpatients presenting at our SDCC, the attending anesthesiologist completed a study survey that was designed to identify: completeness of history; important concerns as judged by the pre-admission nurse; whether the patient was seen in the anesthesia preadmission clinic (PAC) for a consultation; if there was a delay in SDCC, the duration and reasons for the delay; whether in the opinion of the attending anesthesiologist the patient should have had an anesthetic consultation; whether the patient was canceled and the reason for cancellation. RESULTS: A nurse based model for screening all outpatients in a university affiliated tertiary hospital day care unit had an accuracy of 81%, specificity of 86%, sensitivity of 46% and a negative predictive value of 92%. The cancellation rate with this model was 1.4%(8/551) and the case delay rate was 3.4%(19/551). The referral rate to anesthesiology staff was 17.5%(117/668) and the referral rate to the PAC for anesthetic consultation was 5.1%(34/668). CONCLUSIONS: The use of the nurse based model allowed for the efficient use of anesthesia and surgical day care centre resources. The model was better at 'ruling out' patients who do not need to be seen by anesthesiology ahead of the day of surgery rather than 'ruling in' patients who need to be seen by anesthesiology.

Adult↗
PubMed1999

Early and late reversal of rocuronium and vecuronium with neostigmine in adults and children.

UNLABELLED: We investigated the influence of the timing of neostigmine administration on recovery from rocuronium or vecuronium neuromuscular blockade. Eighty adults and 80 children were randomized to receive 0.45 mg/kg rocuronium or 0.075 mg/kg vecuronium during propofol/fentanyl/N2O anesthesia. Neuromuscular blockade was monitored by train-of-four (TOF) stimulation and adductor pollicis electromyography. Further randomization was made to control (no neostigmine) or reversal with 0.07 mg/kg neostigmine/0.01 mg/kg glycopyrrolate given 5 min after relaxant, or first twitch (T1) recovery of 1%, 10%, or 25%. Another eight adults and eight children received 1.5 mg/kg succinylcholine. At each age, spontaneous recovery of T1 and TOF was similar after rocuronium and vecuronium administration but was more rapid in children (P < 0.05). Spontaneous recovery to TOF0.7 after rocuronium and vecuronium administration in adults was 45.7 +/- 11.5 min and 52.5 +/- 15.6 min; in children, it was 28.8 +/- 7.8 min and 34.6 +/- 9.0 min. Neostigmine accelerated recovery in all reversal groups (P < 0.05) by approximately 40%, but the times from relaxant administration to TOF0.7 were similar and independent of the timing of neostigmine administration. Recovery to T1 90% after succinylcholine was similar in adults (9.4 +/- 5.0 min) and children (8.4 +/- 1.1 min) and was shorter than recovery to TOF0.7 in any reversal group after rocuronium or vecuronium administration. Recovery from rocuronium and vecuronium blockade after neostigmine administration was more rapid in children than in adults. Return of neuromuscular function after reversal was not influenced by the timing of neostigmine administration. These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. IMPLICATIONS: These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Although spontaneous and neostigmine-assisted recovery is more rapid in children than in adults, in neither is return of function as rapid as after succinylcholine administration.

Adult↗
PubMed1999

Reflective meniscometry: a non-invasive method to measure tear meniscus curvature.

AIMS: To devise a method to measure tear meniscus curvature by a non-invasive specular technique. METHODS: A photographic system was devised. The system consisted of a camera and an illuminated target with a series of black and white stripes oriented parallel to the axis of the lower tear meniscus. The target was mounted on a flash gun close to the objective of a Brown macrocamera and calibrated using a graduated series of glass capillaries of known diameter, ground down to expose the inner wall. It was then applied to normal human eyes (n = 45) to measure the tear meniscus curvature. A video system was also assessed which provided qualitative online information about the tear meniscus. RESULTS: Using the photographic system, measured values for capillary radii were in excellent agreement with theoretical calculations (r2 = 0.996, p < 0.0001). The radii of curvature of lower tear menisci in normal human subjects (mean 0.365 (SD 0.153) mm, range 0.128-0.736; n = 45) were similar to those reported in the literature. Both systems demonstrated variations in meniscus shape. The video system provided stable images of human menisci over prolonged periods of time and promises to be useful for the analysis of dynamic changes in meniscus volume. CONCLUSIONS: Reflective meniscometry is a non-invasive technique providing quantitative information about tear meniscus shape and volume and of potential value in the study of ocular surface disease.

Calibration↗
PubMed1999

US probes: risk of cross infection and ways to reduce it--comparison of cleaning methods.

After their use at ultrasonography (US) in the intensive therapy unit, probes were used to directly inoculate blood agar plates before and after various cleaning procedures. The uncleaned probes transmitted large numbers of clinically important microbes. Simple cleaning methods were effective in reducing transmission among certain patients: fit patients, double paper wipe; patients at risk of contracting infection, single paper wipe followed by alcohol wipe; patients with a potential source of infection, single paper wipe followed by alcohol wipe.

Bacteria↗
PubMed1999

[Consensus on the diagnosis of multi-system atrophy].

We report the results of a consensus conference on the diagnosis of multiple system atrophy. We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible multiple system atrophy requires one criterion plus two features from separate domains. The diagnosis of probable multiple system atrophy requires the criterion for autonomic failure/urinary dysfunction plus poor levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite multiple system atrophy requires pathological confirmation.

Diagnosis, Differential↗