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Biomedical subjects

J Freeman

Publications and source records attributed to J Freeman.

At least 19 recordsLinked to original sources

Effects of a 5-HT(4) receptor agonist on oesophageal function and gastro-oesophageal reflux: studies using combined impedance-manometry and combined impedance-pH.

BACKGROUND: 5-HT(4) receptor agonists are used as promotility agents of the stomach, small and large intestine. There is limited information on the influence of 5-HT(4) receptor agonists on oesophageal function and gastro-oesophageal reflux. AIM: To evaluate the effects of tegaserod, a 5-HT(4) agonist on oesophageal function using impedance-manometry and postprandial reflux using impedance-pH monitoring. METHODS: Twenty healthy volunteers were enrolled in a double-blind randomized three-period crossover placebo-controlled study. Impedance-manometry and impedance-pH monitoring after a refluxogenic meal were performed at baseline and after 2 days of dosing with tegaserod 6 mg b.d. or placebo. Multichannel intraluminal impedance-EM recorded pressure and bolus transit data during standardized swallows. Multichannel intraluminal impedance-pH monitoring recorded the number of 2-h postprandial acid and non-acid reflux episodes. RESULTS: We found no significant difference in distal oesophageal amplitude when subjects received placebo (median 94.5; range: 53-243 mmHg) or tegaserod (93.6; 43-216 mmHg). Bolus transit time was similar during dosing with placebo (7.1; 5.3-9.4 s) and tegaserod (7.2; 5.9-11.1 s). We observed similar numbers of acid and non-acid reflux episodes during dosing with placebo (5; 0-15 and 3; 0-18, respectively) and tegaserod (2; 0-11 and 4; 0-19, respectively). CONCLUSION: Tegaserod, a 5-HT(4) receptor agonist does not change oesophageal motility and gastro-oesophageal reflux parameters in healthy volunteers.

Adult↗

Clinical-grade myeloma Ag pre-loaded DC vaccines retain potency after cryopreservation.

BACKGROUND: The use of myeloma Ag-loaded mature DC vaccines, cryopreserved in single-use aliquots, is an attractive immunotherapeutic strategy. In this study we investigated the retention of phenotype, viability and potency of DC vaccines after freezing and thawing. METHODS: Plastic-adherent monocytes, derived from a steady-state leukapheresis, were cultured in serum-free media containing GM-CSF and IL-4. DC were loaded on day 6 with myeloma lysate (ML) or idiotype (Id) Ag and keyhole limpet hemocyanin (KLH), induced to mature on day 7 with CD40-ligand and cryopreserved on day 9. Seventeen clinical-scale cultures were evaluated for DC yield, recovery and immunophenotype after potency was validated with allogeneic mixed lymphocyte culture and Ag presentation assays. RESULTS: We produced 88 individual vaccines from 17 clinical-scale cultures. Median DC yield at harvest was 131 x 10(6) (range 37-375 x 10(6)) and median recovery of viable DC after thawing was 69% (range 11-100%). We confirmed viability (7AAD-), phenotype (CD14-, CD83+/CD40+, CD83+/CD80+, CD83+/CD86+, CD83+/CD54+, HLA-DR++) and the ability of the DC to present Ag and stimulate allogeneic T cells post-thawing. DISCUSSION: We have validated a serum-free culture system for the production of DC. Cryopreservation did not interfere with DC activity, allowed time for rigorous quality control (QC) and flexible scheduling of intranodal vaccination, and reduced the time to prepare multiple vaccines.

Antigens, Neoplasm↗

Disposable balloon-based oesophageal motility catheters: comparison with solid-state transducers.

BACKGROUND: Current oesophageal manometry systems use either water-perfused or solid-state pressure transducers. Recently developed single-use disposable catheters use small balloons prefilled with air that transmit the pressure of oesophageal contractions to external transducers. AIM: To compare data obtained from single-use disposable balloon catheters to data from solid-state systems. METHODS: Healthy volunteers, patients with ineffective oesophageal motility and nutcracker oesophagus were studied to include a broad range of pressures. A single-use disposable Clinical Innovations (CI) catheter was placed adjacent to a solid-state Konigsberg Instruments (KI) catheter with pressure transducers at 5, 10, 15 and 20 cm above the lower oesophageal sphincter (LOS). Subjects received liquid and viscous swallows at 30-s intervals. Healthy volunteers received additional sets of swallows while having only one catheter in the oesophagus. RESULTS: When both catheters were present in the oesophagus, no differences were noted between mean pressure measurements in the distal oesophagus and there was good correlation between pressures recorded in response to individual swallows. When present alone in the oesophagus the CI catheter recorded lower mean pressures compared with the KI catheter. Overall there was good agreement in classifying swallows as normal, ineffective and simultaneous. CONCLUSION: Single-use oesophageal manometry catheters are promising alternatives to solid-state manometry systems in measuring intra-oesophageal pressures.

Adult↗

Identification of hiatal hernia by esophageal manometry: is it reliable?

Hiatal hernias are frequently diagnosed during upper endoscopy or barium radiography. They can also be identified based on the typical 'double high pressure zone' or 'double hump' during stationary manometric pull-through. This paper aims to compare manometric and endoscopic identification of hiatal hernias. We retrospectively reviewed records of patients who had an esophageal manometry performed in our laboratory between July 2002 and July 2003. We identified 153 patients (104 females, mean age 56 years) who had both an esophageal manometry and upper endoscopy. The manometric studies were reviewed looking for the characteristic double high-pressure zone characteristic of hiatal hernia. The endoscopic reports were reviewed for the independent identification of an hiatal hernia. Information on race, gender, presence of hiatal hernias, esophagitis, and symptoms during esophagogastroduodenoscopy (EGD) exams was recorded from the reports of patients who had both EGD and manometric studies at our institution. Of the 153 patients with both endoscopy and manometry, 11 (7%) had an hiatal hernia identified by manometry compared to 51 (33%) by endoscopy. Ten (91%) of the manometrically identified hiatal hernias were also seen on endoscopy. Compared to endoscopy (gold standard), esophageal manometry had a sensitivity of 20% and a specificity of 99% for detecting hiatal hernias. Manometric identification of an hiatal hernia is an infrequent finding with low sensitivity but high specificity compared to endoscopy.

Adolescent↗

Increased rate of DNA recovery from United Kingdom epidemic Clostridium difficile PCR ribotype 1 strains stored cryogenically.

We noted that some Clostridium difficile isolates are nonrecoverable after frozen storage and so used molecular typing analysis to characterize DNA from these strains. The recovery rate of C. difficile PCR ribotype 1 was statistically significantly greater than that of other strains. This observation has implications for C. difficile epidemiological studies.

Clostridioides difficile↗

Comparison of the effect of detergent versus hypochlorite cleaning on environmental contamination and incidence of Clostridium difficile infection.

To determine how best to decontaminate the hospital environment of Clostridium difficile, we carried out a cross-over study on two elderly medicine wards to determine whether cleaning with a hypochlorite disinfectant was better than using neutral detergent in reducing the incidence of C. difficile infection (CDI). We examined 1128 environmental samples in two years, 35% of which grew C. difficile. There was a significant decrease of CDI incidence on ward X, from 8.9 to 5.3 cases per 100 admissions (P<0.05) using hypochlorite, but there was no significant effect on ward Y. On ward X the incidence of CDI was significantly associated with the proportion of culture-positive environmental sites (P<0.05). On ward Y the only significant correlation between CDI and C. difficile culture-positive environmental sites was in patient side-rooms (r=0.41, P<0.05). The total daily defined doses of cefotaxime, cephradine and aminopenicillins were similar throughout the trial. These results provide some evidence that use of hypochlorite for environmental cleaning may significantly reduce incidence of CDI, but emphasize the potential for confounding factors.

Aged↗

Intra-rater and inter-rater reliability of gait measurements with CODA mpx30 motion analysis system.

Variations between measurements of clinical outcomes sometimes result from observer errors and are not due to the therapeutic intervention. For the correct interpretation of clinical data it is, therefore, important to ascertain the reliability of the measurement methods used. In the present study we evaluated the test-retest and between observer reliability of gait measurements with the Cartesian Optoelectronic Dynamic Anthropometer (CODA mpx30) motion analysis system. Our findings suggest a better intra-rater and inter-rater reliability of kinetic than kinematic data. Disagreements between the investigators were most marked for the kinematic data, especially the hip angle, and disagreements were least for the spatio-temporal gait parameters. The poor reproducibility of kinematic variables may be due to problems with the accurate placement of markers on the surface anatomical landmarks.

Adult↗

Use of the infant transwarmer mattress as an external warming modality in resuscitation from hypothermia.

Normothermia must be established in drowning victims before death may be declared, as the myocardium may remain resistant to stimulation at subnormal temperatures, and complete neurological recovery from submersion associated hypothermia has been reported. A safe and effective method of external re-warming is described that may prove particularly useful in the paediatric population.

Beds↗

The effects of storage conditions on viability of Clostridium difficile vegetative cells and spores and toxin activity in human faeces.

AIMS: Clostridium difficile is a common nosocomial pathogen and as such diagnostic and research methods may necessitate storage of faecal specimens for long periods, followed by subsequent re-examination. This study investigated the effects of storage conditions upon the viability of this organism and its toxin. METHODS: Three genotypically distinct strains of C difficile (two clinical isolates including the UK epidemic strain, and an environmental isolate) were grown anaerobically at 37 degrees C for 72 hours in a pool of five faecal emulsions. Aliquots of each emulsion were stored at either -20 degrees C (frozen) or 4 degrees C (refrigerated). Emulsions were assayed for viable cells, spores, and cytotoxin titre before storage and at days 1, 3, 5, 7, 14, 28, and 56. An aliquot of each emulsion was also removed, assayed, and replaced in storage at each time point to investigate the effects of multiple freezing/refrigeration/thawing. RESULTS: Neither storage temperature nor multiple cycles of refrigeration/freezing and thawing adversely affected the viability of C difficile vegetative cells or spores. Single and multiple exposures of samples to 4 degrees C had little effect upon the C difficile toxin titre. Toxin titres of multiply frozen and thawed faeces became significantly lower than for refrigerated faeces (p < 0.01) by day 5 of the experiment in two of the three strains, and in all strains by day 28. Toxin titres of singly frozen faeces became significantly lower than for refrigerated faeces (p < 0.01) by day 56 of the experiment in two of the three strains. CONCLUSION: Storage temperature and multiple cycles of freezing (refrigeration)/thawing had minimal effects upon the viability of C difficile or its spores. Storage at 4 degrees C has no discernible effect on C difficile cytotoxin. However, storage at -20 degrees C has a detrimental effect upon C difficile cytotoxin, and multiple cycles of freezing and thawing may further adversely effect toxin titres.

Aged↗

Recall and response of smokers and recent quitters to the Australian National Tobacco Campaign.

OBJECTIVE: To track national population indices of recall and response among smokers and recent quitters to an ongoing national televised anti-smoking campaign in Australia. METHOD: National cross sectional population telephone surveys of adults. MAIN OUTCOME MEASURES: Unprompted recall of advertising; recognition of advertising; campaign attributed encouragement to quit or stay quit; unprompted awareness of smoking related health effects; new learning about smoking and health; and agreement with campaign related attitudes. RESULTS: Campaign advertising continued to be highly memorable over the period of study, with 88% having confirmed recognition in 2000. Campaign advertising was consistently thought by half of smokers who had seen it to make them more likely to quit (49% in 2000). Specific changes between surveys in unprompted awareness of smoking related health effects, new learning about smoking and health, and agreement with campaign related attitudes were observed in relation to the main messages of the advertisements, which were time sensitive according to the year of launch of the advert. The "artery" advertisement was associated with the largest and most consistent positive change in all of these parameters. The proportion of respondents who disagreed that the dangers of smoking had been exaggerated increased significantly from 59% in May 1997 to 68% in November 2000. CONCLUSION: A national campaign using graphic advertising to emphasise the health risks of smoking can make significant population wide contributions to improving new learning about smoking damage and positively influence attitudes about smoking risks.

Adolescent↗

Impact of tobacco tax reforms on tobacco prices and tobacco use in Australia.

OBJECTIVE: To document the impact of changes to tobacco taxes on the range and price of tobacco sold during the period when the National Tobacco Campaign (NTC) was run. DATA SOURCES: Information about brand availability, pack size, and price was extracted from Australian Retail Tobacconist. A retail observational survey was undertaken to monitor actual retail prices. Data on cigarette prices, brands, packet configurations, and outlets from which they were purchased were obtained from the benchmark and three follow up population telephone surveys conducted to evaluate the NTC. METHOD: Data from the three sources were compared to see the extent to which the impact of tax changes had been offset by greater retail discounting and a more concerted effort by consumers to purchase cheaper products. RESULTS: Smokers were unable to cushion themselves from the sharp price increases that occurred during the third phase of the NTC. Both average recommended retail prices of manufactured cigarettes and average actual cigarette prices paid by smokers increased by 25% in real prices. CONCLUSION: The fall in smoking prevalence over the first two phases of the NTC was substantially greater than would be expected due to tax changes alone. The fall in smoking consumption over the first two phases was slightly less than would be expected and in the third considerably higher than would be expected.

Adolescent↗

Laminated microelectrodes: a simple approach to the construction of inexpensive microelectrodes with a variety of geometries.

Designs for reusable microelectrodes, which are easy to assemble and so do not require special technical skills or services for their construction, are presented. Three types of microelectrodes are fabricated by lamination of metal foil, wire, and wire grids, producing microband, microdisk, and a linear array of microdisk geometries. The electrodes themselves do not need to be polished prior to their use but are observed to be slightly recessed from the surrounding insulating surface. Good agreement is observed between experimental steady-state voltammetric results in nonaqueous solutions and the relevant analytical theory for the voltammetric current.

Journal Article↗

Discovery of novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. 4. Structure-activity relationship of substituents on the benzene ring of the cinnamide.

We have shown that p-arylthio cinnamides can inhibit the interaction of LFA-1 and ICAM-1, which is involved in cell adhesion and the inflammatory process. We now show that 2,3-disubstitution on the aryl portion of the cinnamide results in enhanced activity over mono substitution on the ring. The best 2,3-substituents were chlorine and trifluoromethyl groups. Compounds 39 and 40 which contain two CF3 groups have IC(50) values of 0.5 and 0.1 nM, respectively, in inhibiting JY8 cells expressing LFA-1 on their surface, from adhering to ICAM-1. The structure-activity relationship (SAR) was examined using an NMR based model of the LFA-1 I domain/compound 31 complex. One of our compounds (38) was able to reduce cell migration in two different in vivo experiments.

Amides↗

Congenital cystic dysplasia of the rete testis.

Cystic dysplasia of the rete testis (the network of straight seminiferous tubules within the mediastinum testis leading to the efferent ductules) is a rare congenital anomaly. There are only 15 cases reported in the literature to date and only one report of the US findings [1-5]. This report highlights the characteristic appearance of the lesion on ultrasound examination and its association with renal abnormalities in two patients.

Abnormalities, Multiple↗

Adenine phosphoribosyltransferase deficiency and renal allograft dysfunction.

Adenine phosphoribosyltransferase (APRT) deficiency is a rarely diagnosed cause of renal allograft dysfunction. We report the case of a 42-year-old man who presented in 1996 with idiopathic renal failure. Native kidney biopsy showed extensive microcrystalline interstitial nephritis. The patient subsequently underwent a living-related kidney transplant with excellent early graft function. During the next year, however, he had worsening allograft function, and allograft biopsy showed recurrent interstitial nephritis. Further chemical and spectroscopic analysis showed this lesion to be an annular microcrystalline nephritis consistent with APRT deficiency. This diagnosis was confirmed on erythrocyte assay. Treatment with allopurinol and a low-purine diet led to improvement and stabilization of renal function. APRT is a rare cause of renal allograft dysfunction requiring a high index of suspicion for early diagnosis and treatment. Increased physician awareness in the United States may hasten diagnosis and limit the morbidity associated with this disease.

Adenine Phosphoribosyltransferase↗

Retrospective classification of prostate-specific antigen tests: differentiating screening from diagnostic clinical encounters.

To assess the validity of retrospective medical chart review as a method of classifying prostate-specific antigen (PSA) tests as screening or diagnostic services, we reviewed PSA tests ordered at a university hospital (n = 95). PSA tests were reviewed by four raters: medicine resident (RES), oncologist (ONC), urologist (UR), medicine attending (GM)-and the physician who ordered the PSA test (ATTEND) using predefined standardized criteria. Agreement rates by individual rater and ATTEND were 0.79 (GM), 0.80 (ONC), 0.74 (UR), 0.83 (RES), for a composite percent agreement of 0.79. ATTEND incorrectly classified seven tests; exclusion of these tests raised agreement rates to 0.86 (GM), 0.86 (ONC), 0.80 (UR), 0.90 (RES), for a group composite percent agreement of 0.86. Of note, two raters had higher agreement rates when evaluating screening PSA tests than when evaluating diagnostic PSA tests. Standardized criteria applied to medical charts provide a valid method of retrospectively classifying PSA tests.

Adult↗