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Biomedical subjects

A Fox

Publications and source records attributed to A Fox.

At least 91 records · Page 5Linked to original sources
PubMed1996

Absolute identification of muramic acid, at trace levels, in human septic synovial fluids in vivo and absence in aseptic fluids.

This is the first report of a study employing the state-of-the-art technique of gas chromatography-tandem mass spectrometry for absolute identification of muramic acid (a marker for peptidoglycan) at trace levels in a human or animal body fluid or tissue. Daughter mass spectra of synovial fluid muramic acid peaks (> or = 30 ng/ml) were identical to those of pure muramic acid. Absolute chemical identification at this level represents a 1,000-fold increase in sensitivity over previous gas chromatography-mass spectrometry identifications. Muramic acid was positively identified in synovial fluids during infection and was eliminated over time but was absent from aseptic fluids.

Arthritis, Infectious↗
PubMed1995

Do intracarotid barbiturate injections offer a way to investigate hemispheric models of anosognosia?

In a sample of 83 patients counterbalanced for side of temporal-lobe seizure focus, we examined unawareness of hemiplegia upon clearing of the deficit after bilateral sodium amobarbital injections. Unawareness occurred commonly (66%) and with equal frequency following left and right injections. These findings were not moderated by speech dominance, handedness, sex, or side of seizure focus. Unawareness occurred more frequently after injections contralateral to than ipsilateral to the major seizure focus and was related to objective memory performance after contralateral, but not after ipsilateral, injections. Unawareness of drug-induced hemiplegia was related to the functional status of the temporal lobe independently of hemispheric laterality or degree of frontal lobe inactivation as measured by filling of the anterior cerebral arteries.

Adolescent↗
PubMed1995

Antihypertensive effects of moexipril, a new ACE inhibitor, as add-on therapy to nifedipine in patients with essential hypertension.

Moexipril is a new nonpeptide angiotensin-converting enzyme (ACE) inhibitor with an intermediate duration of action. The antihypertensive efficacy and safety of moexipril as add-on therapy to nifedipine retard (20 mg b.i.d) was compared to placebo during 8 weeks in a double-blind trial with a parallel group design. A total of 203 patients with essential hypertension and a sitting diastolic blood pressure (DBP) > or = 95 mm Hg on nifedipine alone were randomly assigned to placebo or moexipril 3.75 mg o.d., 7.5 mg o.d., or 15 mg o.d.. At endpoint, the adjusted mean reductions in DBP from baseline were 6 mm Hg, 9 mm Hg (p < 0.01), and 9 mm Hg (p < 0.05) in the moexipril 3.75 mg, 7.5 mg, and 15 mg groups, respectively, compared to 5 mm Hg in the placebo group. All dosages of moexipril were well tolerated, and the overall percentages of patients who reported adverse experiences were smaller than in the placebo group. We concluded that moexipril as add-on therapy to nifedipine is well tolerated and gives additional antihypertensive effects.

Adolescent↗
PubMed1995

Experimental infection of human nasal mucosal explants with Neisseria meningitidis.

The interaction of Neisseria meningitidis with rhinopharyngeal epithelium was studied by experimental infection of explants of human nasal turbinate mucosa with two wild strains: a fully capsulate case isolate, and an epidemiologically related non-capsulate nasopharyngeal isolate. After incubation for 4 h, epithelial cells of infected explants changed conformation from tall columnar morphology towards cuboidal, and there was increased discharge of mucus globules from goblet cells. By 24 h there was significant damage to infected epithelia, including projection of cells out of the surface, cytoplasmic blebbing and mitochondrial abnormalities. Meningococci were associated with surface non-ciliated cells by 4 h after infection. By 24 h after infection they were associated extensively with all cell types exhibiting damage. There was little association with secreted mucus. In areas of cell damage, penetration between surface cells was observed. Endocytosis into non-ciliated cells was observed in only a minority of explants studied and only in those infected for 24 h. From this intracellular site there was apparent migration to adjacent cells and to intercellular locations. No organisms were observed within or beneath basement membrane collagen in any explants but internalisation into mononuclear phagocytes was observed occasionally.

Cilia↗
PubMed1995

Detection of human cytomegalovirus antigenaemia: a rapid diagnostic technique for predicting cytomegalovirus infection/pneumonitis in lung and heart transplant recipients.

BACKGROUND: New rapid diagnostic techniques offer the opportunity of early diagnosis of human cytomegalovirus (CMV) infection in immunocompromised patients at risk of developing CMV disease. The use of human CMV antigenaemia as a predictor of clinical CMV infection and disease in lung and heart transplant recipients was studied prospectively. METHODS: Twenty three heart and nine lung transplant recipients who survived 40 days were observed by standard CMV surveillance with serological testing, culture, and by sequential testing for CMV antigenaemia. CMV antigenaemia testing is a rapid and quantifiable technique in which a viral lower matrix protein is detected in cytospin preparations of peripheral blood polymorphonuclear leucocytes (PMNLs) by immunofluorescent staining. RESULTS: Eleven patients developed CMV infection and five developed CMV disease (four pneumonitis, one duodenitis). These clinical events occurred at a median of 65 days following transplantation. CMV antigenaemia occurred in 17 patients at a median of 35 days following transplantation. Detection of CMV antigenaemia had a sensitivity of 100%, a specificity of 93.7%, and a positive predictive value of 94.1% for CMV related illness. CMV antigenaemia was positive at a significant interval before the clinical event. High levels of CMV antigenaemia (> 50 CMV antigen positive cells/2 x 10(5) PMNLs) occurred in 11 patients and five of these developed disease. CMV antigenaemia of > 50 CMV antigen positive cells/2 x 10(5) PMNLs had a positive predictive value of 45.5% for disease but a negative predictive value of 100%. Patients with disease had higher levels of antigenaemia than those without disease. CONCLUSIONS: CMV antigenaemia is a rapid diagnostic technique which can identify patients likely to develop CMV disease, potentially allowing early treatment.

Antigens, Viral↗
PubMed1994

Electrospray tandem mass spectrometry for analysis of native muramic acid in whole bacterial cell hydrolysates.

Muramic acid is an amino sugar found in eubacterial cell walls and not elsewhere in nature. This study explored the use of electrospray tandem mass spectrometry (ESI MS/MS) in analysis of underivatized muramic acid in bacterial hydrolysates. Fungal hydrolysates were used as negative controls. The only processing used was hydrolysis in sulfuric acid followed by extraction with an organic base (N,N-dioctylmethylamine) to remove the acid prior to ESI MS/MS analysis. Compared with pure muramic acid, bacterial hydrolysates produced more complex ESI mass spectra, such that the protonated molecular ion at m/z 252 was barely detectable. In contrast, product ion spectra of m/z 252 were identical among pure muramic acid, Gram positive bacteria, and Gram negative bacteria. However, no characteristic product ion spectrum was manifested from m/z 252 in fungal samples. This allowed ready, visual differentiation of bacteria and fungi. Multiple reaction monitoring (MRM) following muramic acid fragmentations (m/z 252-->144 and m/z 252-->126) increased sensitivity and allowed quantitative differentiation when compared with the MRM of the internal standard N-methyl-D-glucamine (m/z 196-->44). ESI MS/MS required minimal sample preparation and allowed rapid sample throughput for analysis of muramic acid in whole bacterial cell hydrolysates.

Cell Wall↗
PubMed1994

Interest in natural family planning among female family practice patients.

OBJECTIVE: Although modern methods of natural family planning (NFP) are effective both to avoid and to achieve pregnancy, relatively few women use these methods. It is not known whether this is due primarily to lack of interest or to other factors. We therefore explored the level of interest in NFP among female family practice patients. METHODS: We mailed information about NFP to 400 female patients between ages 21 and 42 and conducted follow-up interviews by telephone. We excluded 162 women for whom we could not obtain accurate addresses or phone numbers, 68 women we could not reach by telephone, 67 women who were not currently at risk of pregnancy, and 15 women for other reasons. Twenty-eight women refused to participate in the study. Sixty women completed telephone interviews. RESULTS: Forty-three percent of respondents (n = 60) were interested in learning more about NFP, 24% said they were likely to use NFP to avoid pregnancy, and 32% were likely to use NFP to achieve pregnancy. Younger women and women who were Christian but not Catholic and not of a major Protestant denomination were more interested in NFP. CONCLUSION: Some female family practice patients are interested in learning and using NFP.

Adult↗
PubMed1994

Interleukin-1-beta changes the expression of metalloproteinases in the vitreous humor and induces membrane formation in eyes containing preexisting retinal holes.

PURPOSE: Proliferative vitreoretinopathy occurs when cells migrate into the vitreous humor, where they proliferate and produce a membrane composed of extracellular matrix. Interleukin-1-beta (IL-1-beta) may be involved in these processes because it is chemotactic and mitogenic, and it stimulates metalloproteinase production. In the present study, the effects of intravitreally injected IL-1-beta on retinal membrane formation and the associated changes in metalloproteinase content of vitreous humor were examined. METHODS: Rabbit eyes were injected with IL-1-beta in a buffer, with or without the prior creation of retinal holes. Control eyes received the buffer alone or no injection, with or without retinal holes. Animals were examined by slit lamp biomicroscopy and indirect ophthalmoscopy for 1 month. Zymography was performed on a portion of vitreous humor to assess collagenase content, and the remaining tissue was subjected to histologic analysis. RESULTS: Intraocular IL-1-beta induced perilimbal vessel engorgement, keratic precipitates, synechiae, flare, lens deposits, optic disk hyperemia, and granulomatous formations that gradually subsided during the first week. Intravitreal injection of IL-1-beta in eyes with preexisting retinal holes additionally induced membrane formation. Zymographic analysis of vitreous humor from animals sacrificed 24 hours after IL-1-beta injection showed a 100-kd and a 65-kd gelatinase, whereas control vitreous humor contained predominantly a single gelatinase species of approximately 65 kd. Retinal holes did not affect IL-1-beta induction of the 100-kd gelatinase. CONCLUSIONS: IL-1-beta induces a 100-kd gelatinase in the vitreous humor and epiretinal membrane formation in eyes containing preexisting retinal holes. The presence of retinal holes and abnormal production of cytokines may lead to a cascade of events, including aberrant extracellular matrix remodeling, that result in proliferative diseases of the eye.

Animals↗
PubMed1994

What constitutes general surgical training? Evidence from the log books of trainees in one district general hospital.

It is accepted wisdom that surgical expertise in the UK is achieved by virtue of long service, and perhaps not enough genuine training. The average age at appointment to consultant posts in general surgery has risen from 37.0 years in 1978 to 38.0 in 1992. This message has reached the politicians who run the Health Service: at the Association of Surgeons in Training Annual General Meeting in September 1991 Mrs Virginia Bottomley said 'A complaint often made to me is that trainees, particularly surgical trainees, in the UK are over-experienced but under-trained'. Training posts acquire a reputation (good or bad) based on word of mouth, pass rate in examinations, and success in placing trainees into higher grades. Little is known about the relationship between training and operative experience. Log books have been introduced as a compulsory requirement for the Clinical Surgery in General and Intercollegiate Specialty Examinations. This report aims to define the operative experience of trainees at a District General Hospital by analysis of data obtained from their log books. This information has been used to calculate trainee workload in terms of intermediate equivalents (IE) and service equivalent value (SEV).

Education, Medical, Graduate↗
PubMed1993

Event-related potential indices of semantic processing in schizophrenia.

Event-related potentials (ERPs) were recorded while schizophrenic patients and healthy controls read congruous and incongruous sentences in anticipation of a memory test. The schizophrenic group performed more poorly in both recognition memory and cued recall tests. The two groups did not differ in the amplitude of the N400 component of the ERP but the difference between the ERPs to congruous and incongruous sentences persisted longer in the schizophrenic sample. The schizophrenic sample also showed reduced parietal positivity and a reduced effect of congruity on the late positive component that follows N400. Within the schizophrenic sample, measures of attentional impairment and positive thought disorder were correlated with mean amplitude of both the N400 and the subsequent positivity. The results imply that the structure and spread of activation within semantic memory is not impaired in schizophrenia. Rather, impairments appear to lie in processes required to integrate activated information with the current context.

Adolescent↗
PubMed1993

Activation of uterine intraepithelial gamma delta T cell receptor-positive lymphocytes during pregnancy.

Intraepithelial lymphocytes (IEL) of the uterus of non-pregnant sheep were analyzed by single- and two-color flow cytometry. Very few lymphocytes carrying classical B and T cell markers (CD5, surface immunoglobulin) were detected in the uterine epithelial cell suspensions and all IEL expressed the CD8 surface marker although with varying intensities. Three distinct subpopulations were identified including a major (46-56%) population of CD8+CD45R- gamma delta T cell receptor (TcR)-negative cells and approximately equal numbers of CD8+CD45R+ gamma delta TcR- and CD8+CD45R+ gamma delta TcR+ lymphocytes. The same three subpopulations were also present in the interplacentomal areas of the uterus of ewes at a late stage of pregnancy but there was a dramatic increase (60-70%) in the gamma delta TcR+ subpopulation. In addition, a pronounced increase in both size and granularity was observed in the IEL population of pregnant uteri and this was attributed to the gamma delta TcR+ cells. Light and electron microscopic examination of these gamma delta TcR+ IEL revealed an increase in metabolic activity and the formation of exceptionally large cytoplasmic granules and confirmed their restricted localization within the uterine epithelium close to the trophoblast. These results represent for the first time, a clear example of the activation of gamma delta TcR+ cells which is not associated with an ongoing disease process or infection. gamma delta TcR+ cells have recently been observed in the epithelium of the murine reproductive tract and were characterized by their unique homogeneous receptor structure. The present results indicate that these cells may play an important physiological role during pregnancy.

Animals↗
PubMed1993

Recurrent anterior uveitis induced by multiple systemic injections of muramyl dipeptide.

The development of new therapeutic modalities in the treatment of uveitis has been greatly aided by the availability of suitable animal models. The endotoxin model excellently mimics many features of acute anterior uveitis. A new model that exhibits many features of recurrent anterior uveitis is described here. Muramyl dipeptide, MDP, is a synthetic monomer of Gram positive and Gram negative bacterial cell walls. The molecule is highly inflammatory, but unlike endotoxin does not elicit an antibody response. After a single injection (4 hr post-injection), acute anterior segment changes include massive engorgement of peri-limbal blood vessels, anterior chamber flare, fibrin deposits and heterophil (neutrophil) infiltration which subside within 24-48 hr. There is also break-down of the blood-aqueous barrier. With multiple injections the exacerbations and remissions continue to be observed after each injection but the disease progresses to a recurrent form including the development of synechiae and a mononuclear infiltrate into the anterior segment. The ocular changes are paralleled by changes in the bloodstream with recurrent heterophilia. Thus MDP does not elicit ocular or systemic tolerance. This new model of anterior uveitis should allow study of many of the events that occur in recurrent uveitis in man.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1993

P300 indexes thought disorder in schizophrenics, but allusive thinking in normal subjects.

Loosening of thinking as assessed by the Object Sorting Test (OST) has been found in a percentage of normal subjects but in a higher percentage of schizophrenics, and is familially transmitted in both groups. Loosening of thinking in normal subjects is not associated with evidence of impaired function or increased psychopathology, and in recognition of this, it was termed allusive thinking rather than thought disorder. Both OST-assessed loosening and concreteness of thinking were found to be present independently in a high percentage of schizophrenics, so that both were considered to contribute to schizophrenic thought disorder. The presence of OST-assessed loosening in schizophrenics would, therefore, be predicted to correlate partially rather than totally with measures of schizophrenic thought disorder. It has been suggested that OST-assessed loosening in normal subjects is due to a genetically determined reduction in strength of an inhibitory process that limits the spread of activation of semantic associations and results in a predisposition to schizophrenia. The brain event-related potential P300, which is, in part, under genetic control, may index this inhibitory process. Therefore, it was predicted that in normal subjects, P300 would correlate with OST-assessed loosening of associations. If schizophrenic thought disorder is due to a further weakening of this inhibitory process, it can be predicted that P300 in schizophrenics correlates only weakly with OST-assessed loosening of thinking, but more strongly with schizophrenic thought disorder. In a study in which P300 was elicited using a difficult selective attention task with 15 unmedicated schizophrenics and 22 healthy subjects, all three predictions were supported.

Adult↗
PubMed1993

Dilated heart failure in transgenic mice expressing the Epstein-Barr virus nuclear antigen-leader protein.

The Epstein-Barr virus nuclear antigen-leader protein (EBNA-LP) is required for high efficiency B lymphocyte growth transformation by the virus. To test the potential contribution of EBNA-LP to tumorigenesis in vivo, we produced transgenic mice carrying an EBNA-LP cDNA construct, using the widely expressed metallothionein promoter. Expression of EBNA-LP was detected in liver, kidney, heart, lung and spleen. There were no apparent oncogenic consequences of EBNA-LP expression. Unexpectedly however, at ages ranging from about 4 months to over a year, transgenic mice developed symptoms of congestive heart failure, including left ventricular dilatation, right ventricular hypertrophy, left atrial thrombosis, pulmonary oedema and hydrothorax. Fibrillation was not apparent in the electrocardiograph; however a reduction in T-wave amplitude suggested that the development of an abnormality of ventricular repolarization may precede the manifestation of overt symptoms. The highly predictable development of dilated heart failure in these transgenic mice suggests they may be a useful model for the pathophysiological changes associated with human dilated cardiomyopathy.

Animals↗