Functional imaging of the brain in the evaluation of drug response and its application to the study of aging.

Functional neuroimaging techniques including single photon emission computerised tomography (SPECT), positron emission tomography (PET) and functional magnetic resonance imaging (FMRI) can provide insight into the functional connectivity of the human brain in both health and disease, including the effects of aging and drugs on brain function. Neuroimaging measurement techniques can either be direct, using radio-specific ligands, or indirect, using the neurophysiological consequences of pharmacological interventions. Both approaches can be combined with sensorimotor or cognitive activation to examine the interaction between the targeted receptor function and the sensorimotor or cognitive process implicit in the study design.

Changes on storage of polyacid-modified composite resins.

Two polyacid-modified composite resins, Dyract and Compoglass, have been studied for water-uptake on storage in three aqueous media, namely pure water, 0.9% NaCl and 1 M NaCl at 37 degrees C, and the results compared with those of a conventional composite resin, Pekafill. The equilibrium water-uptake of Dyract and Compoglass varied depending on time of cure and ionic strength of the storage medium.

The nose: an underestimated source of Staphylococcus aureus causing wound infection.

For the last fifty years, the nose has been intermittently recognized and targeted as a source of Staphylococcus aureus causing surgical site infection. In London in 1959, Williams and co-workers established for the first time that nasal carriers had increased rates of surgical sepsis compared with non-carriers. For half of these patients, the source was the patient's own nose.

A highly sensitive whole blood natural killer cell assay.

The assessment of natural killer cell activity at baseline and the monitoring of this activity during treatment is important in many diseases especially in patients with cancer and AIDS. An optimised and standardised whole blood chromium release assay is described using K562 cells, the standard target erythroleukaemic cell line. The tumour cell lysis observed using whole blood is comparable to that obtained with the standard 4 h lysis assay using peripheral blood mononuclear cells as effector cells.

Spinal corpora amylacea and motor neuron disease: a quantitative study.

Objective: To test the hypothesis that as there is growing evidence that corpora amylacea, or amyloid bodies, in the CNS are derived primarily from neurons, it might be expected that their numbers in the spinal cord would decline with loss of neurons in motor neuron degeneration as they do in the retina on destruction of ganglion cells by glaucoma.

Methods: The numbers of corpora amylacea were counted in PAS stained transverse sections of the lumbar cord from 27 patients with motor neuron disease and 21 control subjects of similar age and sex mix. The numbers and sizes of corpora amylacea were determined both in the anterior horn grey matter and in the submeningeal white matter regions in each case.

Meta-analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: second report of the Hormones and Urogenital Therapy Committee.

Objective: To evaluate the efficacy of estrogen therapy in the treatment of postmenopausal women with symptoms and signs associated with urogenital atrophy, by meta-analysis of available data.

Methods: We searched the literature (Excerpta Medica, Biosis, MEDLINE, and hand search) for studies published between January 1969 and April 1995. Criteria for inclusion were English-language articles, peer-reviewed original publications, and urogenital atrophy assessed by at least one of the following outcomes: patient symptoms, physician report, pH, or cytologic change.

The influence of nerves on the secretion of immunoglobulin A into submandibular saliva in rats.

1. The influence of sympathetic and parasympathetic nerve stimulations on salivary secretion of immunoglobulin A (IgA) was studied in the submandibular glands of anaesthetized rats by stimulating the nerve supplies with bipolar electrodes. 2.

Influence of acute lung volume change on contractile properties of human diaphragm.

The effect of stimulus frequency on the in vivo pressure generating capacity of the human diaphragm is unknown at lung volumes other than functional residual capacity. The transdiaphragmatic pressure (Pdi) produced by a pair of phrenic nerve stimuli may be viewed as the sum of the Pdi elicited by the first (T1 Pdi) and second (T2 Pdi) stimuli. We used bilateral anterior supramaximal magnetic phrenic nerve stimulation and a digital subtraction technique to obtain the T2 Pdi at interstimulus intervals of 999, 100, 50, 33, and 10 ms in eight normal subjects at lung volumes between residual volume and total lung capacity.

Quality of full and final publications reporting acute stroke trials: a systematic review.

Background And Purpose: Several studies have shown that the quality of reporting of trials throughout medicine is variable and often poor. We report on the quality of the final reports of randomized controlled trials (RCTs) of drug therapies assessed in acute stroke.

Methods: English-language reports published up to the end of 1996 relating to completed RCTs in acute stroke were identified from electronic searches of the Cochrane Stroke Review Group database of stroke trials and the Cochrane Controlled Trials Register (CD-ROM issue 1, 1997, of the Cochrane Library).

The role of theophylline and phosphodiesterase4 isoenzyme inhibitors as anti-inflammatory drugs.

Theophylline has been used for over a century in the treatment of asthma and while it is used principally as a bronchodilator, a number of recent studies have demonstrated potential anti-inflammatory and immunomodulatory activity. Indeed, regular treatment with low-dose theophylline, affords significant clinical benefit at the expense of unwanted side-effects associated with this drug, including headache and vomiting. The mechanism of action of theophylline is unclear, although a significant body of evidence points to an involvement of phosphodiesterase enzyme inhibition.

Biochemical and genetic studies of Caucasian subjects with ethanol-induced flushing reaction.

The prevalence of ethanol-induced flushing was investigated in three different Caucasian student populations, namely Irish, Belgian and English. Approximately 45% of all female subjects reported a flushing reaction, while 33%, 17% and 9%, respectively, of male students reported this reaction. There was a high familial incidence of flushing in all groups, suggesting that a specific gene defect might be involved.

Enhanced T cell proliferation and increased responder frequency following delivery of antigen to the antigen-presenting cell; B cell dependency and use in detection of autoreactive T cells.

Reported frequencies of peripheral blood autoantigen-specific cells in autoimmune diseases are typically low, which could be due to true scarcity or to limitations of in vitro assays. In the present study, antigens were targeted to the antigen-presenting cell (APC) to enhance T cell proliferation, using an antigen delivery system (ADS), consisting of biotinylated anti-IgG, streptavidin and biotinylated antigen. This was able to bind B cells and monocytes and was internalized within 24 hours.

Issues concerning the development of a competency-based assessment system for dentistry.

The issue of standards of competence and assessment is central to professions. For the dental profession there have been suggestions that a change from overall competence to specific fields of competence would be a more suitable mechanism to assess whether an individual was competent. This paper examines the implications of such proposed changes and highlights several key issues, answers to which need to be provided prior to adopting new proposals.

Autoimmunity in diabetic autonomic neuropathy: does the immune system get on your nerves?

Symptomatic autonomic neuropathy is a devastating occasional complication of diabetes mellitus, especially Type 1. Although the full-blown clinical syndrome is not common, dysfunction of the autonomic nerves is detectable in up to 40% of Type 1 diabetic patients but its aetiopathogenesis is poorly understood. There is evidence to suggest that the damage to the autonomic nerves may be immune-mediated.

Endothelial nitric oxide synthase exon 7 polymorphism, ischemic cerebrovascular disease, and carotid atheroma.

Background And Purpose: The role of endothelial nitric oxide synthase (eNOS) in normal physiology suggests that it could be a potential candidate gene for stroke. Reduced eNOS activity could mediate an increased stroke risk through hypertension or independent of hypertension through abnormal vasomotor responses, promoting atherogenesis, or increased platelet adhesion and aggregation. Recently, a common polymorphism in exon 7 of the eNOS gene (894G-->T) has been reported to be a strong risk factor for coronary artery disease.

Expiratory muscle function in amyotrophic lateral sclerosis.

Few data exist concerning expiratory muscle function in amyotrophic lateral sclerosis (ALS). We studied 26 patients with ALS (16 with respiratory symptoms and 10 without) and measured the maximal static expiratory mouth pressure (MEP), the gastric pressure during a maximal cough (Cough Pga), and the gastric pressure after magnetic stimulation of the lower thoracic nerve roots (Tw Pga). These measurements were related to the ability to generate transient supramaximal flow during a cough (cough spikes), to arterialized capillary blood gases, and to inspiratory muscle strength.

The effect of PDGF, TGF-beta and IGF in combination on androgen metabolism by fibroblasts.

The aim of this investigation is to study growth factor combinations (PDGF/IGF PDGF/TGF-beta and TGF-beta/IGF) on the metabolism of 2 androgen substrates 14C-testosterone/14C-4-androstenedione to the matrix stimulatory androgen 5alpha-dihydrotestosterone (DHT). Human gingival fibroblasts in culture were incubated in Eagle's MEM with the radiolabelled substrates and growth factors for 24 h, when the medium was extracted and analysed for radioactive metabolites. When 14C-testosterone was used as substrate, there was an 80% increase in DHT synthesis over controls with the PDGF/IGF combination (n=7; p<0.

A comparative study of iatrogenesis, medication abuse, and psychiatric morbidity in chronic pain patients with and without medically explained symptoms.

We report a case control study comparing patients attending a pain clinic whose symptoms were not considered medically explained (cases) with those whose symptoms were considered medically explained (controls). Principal comparisons were psychiatric morbidity, medication use, and iatrogenic factors assessed by interview, and questionnaire measures of anxiety, depression, functional impairment, coping strategies and pain beliefs. Medically unexplained symptoms were associated with the presence of psychiatric morbidity (odds ratio = 3.

UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10-14 weeks of gestation. Fetal Medicine Foundation First Trimester Screening Group.

Background: Prenatal diagnosis of trisomy 21 currently relies on assessment of risk followed by invasive testing in the 5% of pregnancies at the highest estimated risk. Selection of the high-risk group by a combination of maternal age and second-trimester maternal serum biochemistry gives a detection rate of about 60%. We investigated assessment of risk by a combination of maternal age and fetal nuchal-translucency thickness, measured by ultrasonography at 10-14 weeks of gestation.