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Biomedical subjects

P Jeffery

Publications and source records attributed to P Jeffery.

At least 19 recordsLinked to original sources

Expression of growth hormone secretagogue receptor type 1a, the functional ghrelin receptor, in human ovarian surface epithelium, mullerian duct derivatives, and ovarian tumors.

Ghrelin, the endogenous ligand of the GH secretagogue receptor (GHS-R), is a newly identified, ubiquitously expressed molecule that has been involved in a wide array of endocrine and nonendocrine functions, including cell proliferation. In this context, our group recently reported the expression of ghrelin and its functional receptor, the GHS-R type 1a, in the human ovary and testis as well as several testicular tumors. Ovarian malignancies, however, remain unexplored. Notably, a vast majority of ovarian tumors derive from the surface epithelium, which originates from the celomic epithelium. Considering the proven expression of ghrelin in the human ovary, and its reported effects in the proliferative activity of different cancer cell lines, we aimed at evaluating whether the ovarian surface epithelium as well as related reproductive structures and tumors are potential targets of ghrelin. To this end, expression of GHS-R1a was analyzed by immunohistochemistry in a panel of normal, metaplastic, and neoplastic tissues. Uniform GHS-R1a immunostaining was detected throughout the ovarian surface epithelium. Likewise, ciliated cells within the fallopian tube epithelium showed strong GHS-R1a expression. In contrast, other celomic derivatives, such as endometrium and endocervix, were negative for GHS-R1a immunoreactivity. In keeping with data from normal tissues, inclusion cysts from the surface epithelium expressed GHS-R1a. Similarly, benign serous tumors resembling fallopian tube epithelium were also positive, whereas serous cystadenocarcinomas showed GHS-R1a expression only in highly differentiated specimens. In contrast, other neoplasms, such as mucinous cystadenomas and cystadenocarcinomas, endometrioid tumors, clear cell carcinomas, and Brenner tumors, did not express GHS-R1a. In conclusion, our results demonstrate that the ovarian surface epithelium and related tumors are potential targets for systemic or locally produced ghrelin because they express the functional type 1a GHS-R. Considering the relevant role of the ovarian surface epithelium in key physiological events (such as ovulation) and neoplastic transformation of the ovary, the potential actions of ghrelin in those phenomena merit further investigation.

Cervix Uteri↗

Management of extra-cranial vertebral artery injuries.

OBJECTIVES: To review the management of vertebral artery injuries, and the impact of pre-operative angiography. MATERIALS AND METHODS: A retrospective review was conducted of all patients with vertebral artery (VA) injuries admitted to Groote Schuur Hospital, Cape Town between January 1987 and December 2002. Patients presenting with uncontrolled active bleeding or haemodynamic instability with a poor response to resuscitation were taken immediately to surgery. Stable patients, including those who stabilised after simple resuscitation, with evidence of a vascular injury (a bruit or a large haematoma) or trans-cervical gunshot wounds, underwent routine aortic arch and selective angiography. RESULTS: One hundred and one patients with vertebral artery injuries were included in the study. Ninety-two patients sustained penetrating injuries (41 gunshot, 51 stab), three were iatrogenic and six due to blunt trauma. Angiography was performed as the primary investigation in 88 patients, while seven patients had angiography following surgery. Thirty-nine vertebral artery occlusions, 11 arteriovenous fistulae, two intimal injuries and 36 false aneurysms were identified. Thirty-three radiological interventions were performed. There were 22 associated vascular injuries in 16 patients, 27 nerve injuries in 25 patients, 11 osseous injuries in nine patients and eight aerodigestive injuries. Seven patients died. CONCLUSIONS: Angiography and intervention is of great benefit in the diagnosis and management of traumatic vertebral artery injuries. Angiography often avoids unnecessary exploration and permits endovascular treatment.

Adult↗

Another cause for bilateral haemorrhagic otorrhoea following trauma.

Bleeding from the external auditory meatus (haemorrhagic otorrhoea) following head trauma is usually attributed to a basal skull fracture. However, it may also result from unsuspected facial trauma. We describe a case that highlights an usual but important differential diagnosis for bilateral haemorrhagic otorrhoea.

Adult↗

Inflammation and remodeling in the adult and child with asthma.

Inflammation and remodeling are characteristic features of the conducting airways in asthma, but the relationships between inflammation, inappropriate remodeling, bronchial hyperresponsiveness, and reduced pulmonary function are still unclear. In both adults and children with asthma, there are structural changes of the conducting airways that include injury and loss of the surface epithelium, thickening of the reticular basement membrane, increases of underlying collagen, blood vessels, and airway smooth muscle, and plugging of the airways by exudate. Bronchial biopsies obtained from persons with mild stable asthma already demonstrate the presence of inflammation. Many of the inflammatory and structural changes begin early in childhood. Whereas corticosteroids markedly reduce many aspects of inflammation, it is not known whether and how they affect the changes associated with airway wall remodeling. Leukotriene receptor antagonists appear to be antiinflammatory and able to reduce the proliferation of bronchial smooth muscle.

Adrenal Cortex Hormones↗

Variation in the measurements of basement membrane thickness and inflammatory cell number in bronchial biopsies.

We do not have an estimate of how much tissue is needed for a reliable measure of bronchial epithelial reticular basement membrane (RBM) thickness or for counts of inflammatory cells. An assessment of the frequency distribution and variance of data from repeat measurements of RBM thickness and biopsy section inflammatory cell counts in cases with asthma (n=6), chronic obstructive pulmonary disease (COPD; n=5), and normal healthy subjects (n=7) was made. Tissue sections were stained with haematoxylin and eosin or by immunohistochemistry for EG2, mast cell tryptase and CD3-positive cells. Measurements of RBM thickness in individuals followed a log-normal distribution. For a precision of approximately +/-15%, 31-45 measurements were required. In contrast, inflammatory cell counts for each individual did not follow a normal distribution. There was high variance such that the cumulative weighted mean did not become stable until at least 5-10 mm of tissue underlying the RBM had been included. In conclusion multiple measurements of reticular basement membrane thickness or tissue section cell counts should be made for each individual in studies of bronchial biopsies. It is recommended that reticular basement membrane thickness should be measured at 20 mm intervals over a 1 mm reticular basement membrane length and that a zone beneath it of at least 5-10 mm of reticular basement membrane should be included for counts of inflammatory cells.

Adult↗

Structural alterations and inflammation of bronchi in asthma.

The structural and inflammatory changes occurring in the bronchi of asthmatics have been examined in specimens from subjects dying in status asthmaticus and from bronchial biopsies of subjects with mild asthma. Histological changes in the bronchi of asthmatics include shedding and damage of the airway surface epithelium and thickening of the reticular basement membrane. Exposure of an asthmatic subject to an allergen results in an immediate allergic response characterised by mast cell degranulation. This may be followed by a late-phase response involving eosinophil degranulation and differentiation of a myofibroblast phenotype which may be the precursor of increased amounts of bronchial smooth muscle present in chronic severe asthma. These changes are accompanied by vasodilatation, vascular congestion and consequent oedema, and result in thickening of the airway wall and reduction of the airway lumen. Mucus secretion further increases airflow resistance and, in conjunction with an inflammatory exudate, forms tenacious airway plugs which are characteristic of severe life-threatening attacks.

Asthma↗

Anti-inflammatory effects of low-dose oral theophylline in atopic asthma.

Theophylline, in addition to its bronchodilator effect, may attenuate inflammation in asthma. We did a double-blind placebo-controlled study of the effect of oral theophylline on the inflammatory response of the bronchial mucosa to inhalation of allergen in 19 atopic asthmatic subjects. Bronchoscopy and bronchial biopsy were done 24 hours after allergen inhalation before and after six weeks of treatment with oral slow-release theophylline, 200 mg 12 hourly. The mean serum concentration was 36.6 mumol/L, which is below the currently-accepted therapeutic range. After treatment with theophylline there was a significant reduction in the number of EG2-positive activated eosinophils (5.9 before and 2.1 after treatment, Wilcoxon signed rank p < 0.05) and total eosinophils (16.7 before and 7.6 after treatment, p < 0.05) beneath the epithelial basement membrane. We conclude that low-dose oral theophylline attenuates airway inflammatory response to allergen inhalation in atopic asthma.

Administration, Oral↗

Elevated medial-frontal cerebral blood flow in obsessive-compulsive patients: a SPECT study.

Regional cerebral blood flow was measured with single photon emission computed tomography in 10 obsessive-compulsive patients and eight comparison subjects. The patients had a significantly higher ratio of medial-frontal to whole cortex blood flow; this was unrelated to symptom severity but was correlated negatively with anxiety. No differences in orbital-frontal blood flow were found.

Adolescent↗

Clinical applications of positron emission tomography.

Positron emission tomography (PET) has been used extensively as a research tool in the investigation of human physiology and pathology for over a decade. By labelling suitable compounds (for example, glucose, amino acids, ammonia, DOPA or drugs) with positron emitting isotopes which are then administered in tracer amounts, the blood flow, metabolism and even the cell receptor or neurotransmitter distributions may be assessed in vivo. Advances in PET technology and experience now make PET a powerful clinical diagnostic tool, enabling investigation of disease at a molecular level, even in the absence of anatomical abnormalities apparent on computerised tomography (CT) or magnetic resonance imaging (MRI). Clinical PET is already utilised in the management of patients with epilepsy, cerebrovascular and cardiovascular disease, dementia and a wide variety of oncological applications. PET will become more widely available shortly in the UK, with the opening of centres such as the Guy's and St Thomas's Clinical PET Centre in 1992. It will therefore become increasingly important that clinicians are aware of those specific areas in which PET may be the investigation of choice to optimise patient diagnosis, treatment and/or follow-up. This review will endeavour to explain briefly the principles of the PET technique, and then outline those areas where PET has already had an impact on patient management in comparison with the more widely available diagnostic tests, finally outlining promising areas where PET may become more clinically useful in the future.

Coronary Disease↗

Pulmonary embolism.

Contemporary concepts in the diagnosis, treatment and natural history of pulmonary embolism are reviewed, and a practical rationale for investigation and therapy is outlined.

Acute Disease↗

Female infanticide and amniocentesis.

Clinical services offering amniocentesis to inform women of the sex of their foetuses have appeared in North India in the past 10 years. They fit into cultural patterns in which girls are devalued, and some authors have seen direct links between female infanticide (assumed to have been eradicated by 1900), female neglect leading to higher infant and child mortality rates for girls, and 'female foeticide'. This paper contributes to this debate by presenting some material on the nature of female infanticide, the cultural setting of childbirth and decision-making with respect to fertility and child mortality, largely drawn from a recent research project in Bijnor District, in Uttar Pradesh, North India.

Amniocentesis↗

A comparative randomized trial of heparin versus streptokinase in the treatment of acute proximal venous thrombosis: an interim report of a prospective trial.

A controlled, prospective study comparing streptokinase and heparin treatment has been completed in 51 patients presenting with acute proximal venous thrombosis of less than 8 days' clinical duration. Patients were studied by means of pre-treatment, post-treatment, 3- and 12-monthly phlebography and pulmonary perfusion scanning and were followed up at 3-monthly intervals. Of the 26 patients randomized to receive streptokinase, therapy was stopped in 3 because of complications. Phlebography 5 days after starting treatment showed 80--100 per cent lysis in 17 of the 23 patients who completed the course of streptokinase. Two patients later developed partial rethrombosis. One patient developed an asymptomatic pulmonary embolus during treatment. During follow-up (mean 19 months) only 1 of the 17 patients with 80--100 per cent lysis developed postphlebitic symptoms, 3 patients died of unrelated causes and 1 patient was lost to follow-up. In patients randomized to heparin therapy no significant lysis was achieved in any of the 25 patients and only 2 of these patients were found to have asymptomatic legs on follow-up. Two patients in this group died and autopsy confirmed massive pulmonary embolus during treatment. These data suggest that streptokinase is superior to heparin in the treatment of acute proximal venous thrombosis of less than 1 week's clinical duration especially if the thrombus is largely non-occlusive. It must be stressed that in order to avoid the bleeding complications of thrombolytic therapy, streptokinase must not be used within 10 days of major surgery, or even longer after vascular, neurosurgical or eye operations.

Adult↗