bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of the sonologist in a sonographer‐based practice
Authors: Ramsay Philippa A , Fracchia Carla A
Published: March 2003

In many foetal medicine units and private practices, sonographers have gained considerable responsibility and independence. Still, there is a wide divergence of opinion as to their proper role, and to the role of the reporting doctor. The present study examines the role of the sonologist in three sonographer‐based obstetric and gynaecological ultrasound practices. During a 25‐day period, 14 sonographers filled out a questionnaire for each patient they scanned. Questions included indication for scan, whether or not and why the patient was scanned and/or seen by a sonologist, and abnormalities found. Information regarding 700 patients was obtained. Forty‐eight patients were excluded because they were also booked to see a doctor. Of the remaining 652 patients, 74.5% had obstetric indications and 25.5% had gynaecological indications. Ten per cent of all patients scheduled to be scanned only by a sonographer also needed to be scanned by a sonologist, and 34.5% of all patients had contact with a doctor unexpectedly, most commonly to explain findings or arrange treatment and tests. In conclusion, in a sonographer‐based practice the sonologist is often required to provide direct patient care beyond simple report writing. Therefore optimal patient management would require an on‐site sonologist.
Appendiceal rupture during pelvic ultrasound examination
Authors: Styles C , Anderson Jem
Published: March 2003

A case of rupture of the appendix during pelvic ultrasound is presented.
Ultrasound of soft‐tissue masses: Pitfalls in interpretation
Authors: Doyle Anthony James , Miller Mary V , French J Gary
Published: March 2003

A review of 43 patients with soft‐tissue tumours identified from a tumour registry showed a 23% rate of incorrect initial diagnosis by ultrasound imaging. Seven patients, five with malignant tumours, suffered a delay in diagnosis (ranging up to 6 months) as a result. The most common error was to mistake a solid tumour for a haematoma. Caution is recommended in the interpretation of ultrasound of soft‐tissue masses, particularly with regard to the erroneous diagnosis of haematoma.
Radiological–pathological correlation: Alveolar pattern
Authors: Stahl Jürgen , Sage Michael R
Published: March 2003

This review summarizes important pathological lesions of the lung that typically present radiographically with an ‘alveolar pattern’. For each entity, the latest findings as to its pathogenesis, aetiology and pathology are reviewed in the introductory remarks. We then present the typical radiological appearances alongside macroscopic and microscopic pathological photographs. It is hoped that the parallel presentation of radiological image with the pathology will enhance the understanding of the diverse range of diseases the aevolar pattern comprises.
Inflammatory pseudotumour of the liver
Authors: Baillie Mandy , Holden Andrew
Published: March 2003

A case of inflammatory pseudotumour of the liver is presented. The clinical, radiological and pathological findings are described and a brief discussion of this rare but important condition is presented.
Odontoid fracture following an epileptic seizure
Authors: Torreggiani William C , Lyburn Iain D , Harris Alison C , Nicolaou Savvas
Published: March 2003

Fractures of the thoracic and lumber spine are well recognized following an epileptic seizure. Fractures of the cervical spine are not. The rare occurrence of a displaced odontoid fracture type 2, secondary to a grand mal seizure is presented. To our knowledge, this association has not been described previously in the English literature.
Use of endoscopic mucosal clips in radiotherapy planning for oesophageal carcinoma: A series of three cases
Authors: Hui Andrew , Abi‐Hanna David , Rae Robert , Delaney Geoff
Published: March 2003

This paper describes the technique of placing endoscopic mucosal clips to localize oesophageal carcinoma and hence facilitate radiotherapy planning. This technique has been used on three patients in our centre. One was treated radically with external beam radiotherapy and two were treated palliatively (retreatment) with intraluminal brachytherapy. Mucosal hemoclips were placed at the time of endoscopy to indicate the superior and inferior extent of the tumour. The clips provided a radiologically‐recognisable marker of the tumour extent and were visible on simulation films or planning CT scans. The radiation portal included the tumour as demarcated by the clips with an adequate margin. There were no complications related to the placement of the clips. All patients completed the radiotherapy course as planned.
Lumbar artery pseudoaneurysm following renal biopsy: Treatment with ultrasound‐guided thrombin injection
Authors: Ramsay Duncan W , Marshall Martin
Published: March 2003

latrogenic pseudoaneurysms are usually seen following arterial catheterization. However, we describe a case of a 23‐year‐old woman who developed a pseudoaneurysm of a lumbar artery following renal biopsy. In view of her progressing renal failure, arterial embolization was felt to be inappropriate, and although the pseudoaneurysm could be seen ultrasonically, guided compression could not be applied because of the location of the aneurysm deep to the lumbar musculature. Hence, the pseudoaneurysm was thrombosed by percutaneous ultrasound‐guided injection of thrombin directly into the pseudoaneurysm sac. This resulted in immediate thrombosis of the aneurysm and no recurrence on follow‐up imaging. Thrombin injection for femoral artery pseudoaneurysms following catheterization is becoming more widely accepted, and our case demonstrates that this technique might be applied to pseudoaneurysms elsewhere in the body.
Murray Valley encephalitis: Case report and review of neuroradiological features
Authors: Kienzle N , Boyes L
Published: March 2003

We report on a child with diffuse symmetrical thalamic enlargement and signal increase on MRI, representing changes caused by Murray Valley encephalitis (MVE). Very little has previously been reported on the neuroradiological findings of MVE, also known as Australian encephalitis. It is endemic to tropical North Australia, particularly Western Aus­tralia and the Northern Territory, but can occur in other parts of Australia. The last epidemic was in south‐eastern Australia in 1974. Australian encephalitis is the second most serious acute viral encephalitis to be encountered in Australia. Clinicians need to be aware of MVE in this era of ever‐increasing travel. Our aim is to highlight these finding and further define the neuroradiological features.
Frontal recess air cells: Spectrum of CT appearances
Authors: Coates Mark H , Whyte Andrew M , Earwaker John WS
Published: March 2003

The CT appearances of frontal recess air cells is reviewed.
SIGNALLING AND GENE REGULATION BY UREA AND NaCl IN THE RENAL MEDULLA
Authors: Cohen David M
Published: March 2003

1. Cells of the mammalian renal medulla are routinely subjected to an enormously elevated and labile ambient osmolality as a consequence of the renal concentrating mechanism. The present review focuses on the most recent advances in hyperosmotic solute‐mediated signal transduction and regulation of gene transcription in cells of the kidney medulla.

2. On the basis of osmolality alone, NaCl and urea are the principal renal medullary solutes.

3. Urea, which is membrane permeant, activates transcription of immediate‐early genes via an extracellular signal‐ regulated kinase (ERK)/Elk‐1‐dependent pathway. Urea also activates multiple effectors characteristic of a receptor tyrosine kinase‐like signalling cascade.

4. In contrast, the functionally impermeant solute NaCl activates transcription of tonicity responsive genes (principally genes encoding proteins essential for osmolyte uptake or synthesis) via a unique consensus element contained within their 5′ flanking sequences.

5. An activity exhibiting tonicity inducible sequence‐specific interaction with this DNA element has been identified.

6. Hypertonicity, like thermal stress, activates transcription of genes encoding heat shock proteins. The relationship between signalling events leading to tonicity mediated and heat shock‐mediated gene transcription remains to be established.
ENDOTHELIN‐1 AS A MEDIATOR IN CARDIOVASCULAR DISEASE
Authors: Kelly John J , Whitworth Judith A
Published: March 2003

1. Brachial artery infusion of endothelin (ET)‐1 causes transient vasodilatation followed by sustained vasoconstriction of the forearm vascular bed, whereas ET‐1 antagonists cause sustained vasodilatation. These data suggest that ET‐1 contributes to basal vascular tone.

2. Systemic infusion of ET‐1 increases blood pressure and total peripheral vascular resistance and reduces heart rate and cardiac output. The renal and pulmonary circulations are particularly sensitive to the vasoconstrictor effects of ET‐1. Systemic infusion of the ETA/B receptor antagonist TAK‐044 reduces mean arterial pressure and peripheral vascular resistance.

3. Plasma ET‐1 concentrations are not elevated in essential hypertension; however, insulin resistance may be a major determinant of plasma ET‐1 concentrations. Vascular sensitivity to ET‐1 is normal or may be increased in essential hypertension.

4. Plasma ET‐1 concentrations are increased in moderate and severe heart failure and are correlated with clinical and haemodynamic measures of severity. Endothelin‐1 contributes to increased vascular tone in cardiac failure.

5. Plasma ET‐1 concentrations increase following myocardial infarction and persistent elevation predicts an increased mortality within the subsequent 12 months.

6. Preliminary data suggest that interventions that reduce the activity of the endothelin system may have a beneficial effect in heart failure and myocardial infarction.
REDUCTION OF HUMAN RECOMBINANT TYPE II PHOSPHOLIPASE A2 AND PROSTAGLANDIN F2α RELEASE BY MICROTUBULE DEPOLYMERIZING AGENTS
Authors: Munns Mj , King Rg , Rice Ge
Published: March 2003

1. The present study examines the effects of the microtubule depolarizing agent colchicine on secretory type II phospholipase A2 (PLA2) function in Chinese hamster ovary (CHO) cells that specifically overexpress human type II PLA2 and the effect of both colchicine and tubulazole on the release of type II PLA2 and prostaglandin (PG) F2α from human placental explants.

2. Significant suppression by colchicine (0.01–10 μmol/L) of PLA2 activity (P < 0.00001), immunoreactive type II PLA2 (irPLA2; P < 0.00001) and PGF2α release (P < 0.01) was observed in medium from overexpressing CHO cells. These effects were significantly reduced (P < 0.0001) in the presence of 10 μmol/L taxol, an agent that prevents depolymerization of microtubules. The addition of 30 μmol/L arachidonic acid significantly reduced (P < 0.0001) the inhibition of PGF2α production in CHO cell lines.

3. The addition of 1 μmol/L colchicine to human placental explants for 24 h significantly reduced irPLA2 (P < 0.00001) and PGF2α production (P < 0.00001). Similarly, 1 μmol/L tubulazole significantly blocked irPLA2 (P < 0.001) and PGF2α (P < 0.0001).

4. At 10 μmol/L, taxol significantly reduced irPLA2 inhibition by colchicine (n = 8; P < 0.05) and tubulazole (n = 8; P < 0.05). Similarly, taxol significantly reduced the reduction in PGF2α production caused by colchicine (P < 0.001) and by tubulazole (P < 0.001).

5. These results suggest that integrity of the microtubule system is required for PLA2 function and the subsequent production of pro‐inflammatory mediators.
REGULATION OF CASPASE ACTIVATION IN APOPTOSIS: IMPLICATIONS IN PATHOGENESIS AND TREATMENT OF DISEASE
Authors: Kumar Sharad
Published: March 2003

1. Apoptosis is an essential process to remove excess, unwanted and harmful cells and maintain homeostasis. One of the key steps in apoptosis is activation of a group of proteases termed caspases.

2. Caspases are cysteine proteases that cleave their substrates after an aspartate residue. Approximately one dozen such proteases have been cloned during the past few years. While some caspases are largely responsible for the proteolytic processing of proinflammatory cytokines, such as interleukin (IL)‐1β, others are directly involved in the execution of apoptosis.

3. Once apoptotic upstream caspases are activated in response to specific apoptotic stimuli, they can activate the downstream or effector class of caspases. Most proteins that are cleaved during apoptosis leading to the characteristic apoptotic morphology are targeted by the downstream caspases. The cleavage of these proteins by caspases can be either an activating or inactivating event for the function of a protein; however, in most cases, it contributes to the apoptotic phenotype of the cell.

4. Because caspase cleavage is the initiating event in most forms of apoptosis, it is a tightly controlled process with many checks and balances. An understanding of the regulation of caspases is providing novel ways for therapeutic intervention to modulate apoptotic behaviour of cells in many diseases that arise due to inappropriate apoptosis.

5. The present article will endeavour to discuss recent advances in our understanding of caspase regulation and will elaborate on how this knowledge is being used in the development of new classes of therapeutic molecules that can be used for the treatment of human ailments.
EFFECTS OF HEPARIN ON VASCULAR DYSFUNCTION IN DIABETIC RATS
Authors: Oturai Peter S
Published: March 2003

1. Treatment with heparin has beneficial effects in diabetic nephropathy. The occurrence of increased urinary albumin excretion in diabetic patients reflects general vascular dysfunction, including increased transcapillary permeability of macromolecules. The aim of the present study was to evaluate the effects of heparin on vascular dysfunction in diabetic rats.

2. Male Sprague‐Dawley rats were used in two studies. Diabetes was induced by 65 mg/kg, i.v., streptozotocin. In one study, diabetic rats were dosed subcutaneously with different heparin fractions for 8 months and the transcapillary escape rate of albumin (TERalb) was measured in anaesthetized animals. In the other study, heparin was given for 6 weeks, followed by tissue albumin clearance measurements in awake rats. Normal and diabetic rats receiving saline served as controls.

3. Blood glucose did not differ among the diabetic groups and ranged from 22 to 26 mmol/L. The mean (±SD) TERalb was increased by diabetes compared with values in normal rats (17.5±3 vs 14.1±3.3%/h, respectively). Neither unfractionated nor low molecular weight heparin significantly affected this increase. [131I]‐Albumin clearance was significantly increased in diabetic rats in the eye, skin and skeletal muscle tissues compared with normal rats (0.17–0.40 vs 0.1–0.23 μL plasma/g per min). Low molecular weight heparin treatment did not affect the increased organ albumin clearance.

4. In conclusion, heparin treatment does not affect diabetes‐induced vascular dysfunction as expressed by increased TERalb and clearance of albumin in rats.
INTERACTION BETWEEN ENDOTHELIN AND ANGIOTENSIN II
Authors: Phillips Paddy A
Published: March 2003

1. Angiotensin II (AngII) and endothelin (ET) stimulate cardiac hypertrophy in vitro and in vivo. Also AngII stimulates ET production.

2. In order to investigate whether AngII produces its cardiac hypertrophic effects through stimulating ET production which acts on the ETA receptor, male Sprague‐Dawley rats (6–8 weeks of age) received an intravenous infusion of AngII at 0, 100 or 200 ng/kg per min via Alzet osmotic minipumps and jugular venous catheters for 7 days (n = 12 per dose). Half of the rats in each group received the selective ETA receptor antagonist BMS 193884 25 mg/kg per orally and the other half received the vehicle daily.

3. Telemetrically measured mean arterial pressure (MAP) rose with the 200 ng/kg per min dose of AngII (P = 0.0001). The ETA receptor blockade lowered MAP in all groups (P = 0.011). Left ventricular weights increased only in the 200 ng/kg per min AngII infusion rats (P = 0.04). There was no effect of ETA receptor blockade on left ventricular weights.

4. These results suggest that AngII causes left ventricular hypertrophy not only in association with a pressor response but also when MAP was lowered with ETA blockade to control levels, suggesting a non‐pressor effect of AngII on cardiac hypertrophy. Also, ET, acting via ETA receptors, does not mediate the hypertrophic effect of AngII in this model.
EFFECT OF STEROID HORMONES ON BLOOD PRESSURE
Authors: Dodic M , Wintour Em , Whitworth * JA , Coghlan Jp
Published: March 2003

1. There is considerable evidence to support the idea that steroid hormones have the potential to increase blood pressure that may not always be via ‘classical’ mineralocorticoid or glucocorticoid action.

2. Epidemiological studies, together with the evidence from studies in animals, proposed the link between an adverse intra‐uterine environment (i.e. undernutrition or excess exposure to glucocorticoids) and the early onset of cardiovascular and metabolic diseases later in life.

3. We tested this by treating pregnant ewes (and foetuses) with excess steroid early in pregnancy. The mean ages at which the prenatal exposure to glucocorticoid (dexamethasone 0.48 mg/h for 48 h) occurred were 22±0.4 to 29±0.4 days (prenatal treatment group 1; PTG1) and 59±2 to 66±2 days (PTG2), respectively. Basal blood pressures and hormones and the vascular responsiveness to graded doses of angiotensin II and noradrenaline, or to a 5‐day adrenocorticotropin hormone treatment (ACTH), in lambs at 4, 10 and 19 months of age were studied.

4. Basal mean arterial pressure in PTG1 group (80±1 mmHg at 4 months; 83±1 mmHg at 10 months; and 89±1 mmHg at 19 months; n = 6) was significantly different (P < 0.05 in all groups) from that in the control group of lambs (74±2 mmHg at 4 months; 76±1 mmHg at 10 months; and 81±1 mmHg at 19 months; n = 7). Prenatal glucocorticoid exposure did not alter vascular responsiveness to noradrenaline, angiotensin II and ACTH in these sheep at any of the ages studied.

5. These results suggest that foetal exposure to maternal dexamethasone during defined developmental stage or ‘window’ programmes elevated blood pressure, which persists later in life.
Troponin T In The Coronary Sinus And Percutaneous Transluminal Coronary Angioplasty Related Myocardial Injury
Authors: Katoh Harumi , Shimada Toshio , Sano Kazuya , Inoue Shin‐ichi , Kitamura Jun , Sakane Takeshi , Murakami Yo , Ishibashi Yutaka , Karino Kenji , Masuda Junichi
Published: March 2003

1. Myocardial injury has been shown to be associated with successful percutaneous transluminal coronary angioplasty (PTCA). The present study was designed to determine whether uncomplicated successful PTCA results in myocardial injury by measuring coronary sinus (CS) cardiac troponin T (cTnT).

2. We measured cTnT in the CS and the femoral vein (FV) in 16 patients with stable angina pectoris who underwent uncomplicated PTCA for stenotic lesions of the left anterior descending artery. Blood samples were drawn from both the CS and FV before and immediately after PTCA and every 4 h for the next 12 h.

3. All patients had chest pain and electrocardiographic ST segment elevation or depression during balloon inflation and higher peak elevation of cTnT in the CS than in the FV (0.054±0.059 vs 0.036±0.022 ng/mL; P < 0.05). However, all CS cTnT levels were within the normal range over the 12 h period.

4. The fact that CS cTnT measurements showed no evidence of uncomplicated PTCA‐related myocardial injury led us to conclude that uncomplicated successful PTCA does not cause myocardial injury.
RENOMEDULLARY INTERSTITIAL CELLS: A TARGET FOR ENDOCRINE AND PARACRINE ACTIONS OF VASOACTIVE PEPTIDES IN THE RENAL MEDULLA
Authors: Zhuo Jia Long
Published: March 2003

1. The renal medulla plays an important role in regulating body sodium and fluid balance and blood pressure homeostasis through its unique structural relationships and interactions between renomedullary interstitial cells (RMIC), renal tubules and medullary vasculature.

2. Several endocrine and/or paracrine factors, including angiotensin (Ang)II, endothelin (ET), bradykinin (BK), atrial natriuretic peptide (ANP) and vasopressin (AVP), are implicated in the regulation of renal medullary function and blood pressure by acting on RMIC, tubules and medullary blood vessels.

3. Renomedullary interstitial cells express multiple vasoactive peptide receptors (AT1, ETA, ETB, BK B2, NPRA and NPRB and V1a) in culture and in tissue.

4. In cultured RMIC, AngII, ET, BK, ANP and AVP act on their respective receptors to induce various cellular responses, including contraction, prostaglandin synthesis, cell proliferation and/or extracellular matrix synthesis.

5. Infusion of vasoactive peptides or their antagonists systemically or directly into the medullary interstitium modulates medullary blood flow, sodium excretion and urine osmolarity.

6. Overall, expression of multiple vasoactive peptide receptors in RMIC, which respond to various vasoactive peptides and paracrine factors in vitro and in vivo, supports the hypothesis that RMIC may be an important paracrine target of various vasoactive peptides in the regulation of renal medullary function and long‐term blood pressure homeostasis.
Time‐Course Of Changes In Hepatic Lipid Peroxidation And Glutathione Metabolism In Rats With Carbon Tetrachloride‐Induced Cirrhosis
Authors: Cabré M , Camps J , Paternáin Jl , Ferré N , Joven J
Published: March 2003

1. The aims of the present study were to assess: (i) the temporal relationships between hepatic lipid peroxidation, changes in the glutathione detoxification system and the onset/development of cirrhosis in CCl4‐treated rats; and (ii) the effects of oral zinc administration on these parameters.

2. Cirrhosis was induced in 120 rats by intraperitoneal injections of CCl4 twice a week over 9 weeks. One hundred and twenty additional animals were used as controls. Both groups were further subdivided to receive either a standard diet or one supplemented with zinc. Subsets of 10 animals each were killed at weeks 1, 2, 3, 5, 7 and 9 from the start of the study.

3. Induction of cirrhosis produced a decrease in the components of the hepatic glutathione anti‐oxidant system: glutathione transferase activity decreased from week 1, the concentration of reduced glutathione (GSH) decreased from week 5 and glutathione peroxidase (GPx) activity decreased from week 7. This impairment was chronologically related to an increase in free radical generation. Hepatic lipid peroxidation was significantly correlated with GPx activity (r = – 0.47; P < 0.001) in CCl4‐treated rats. Zinc administration did not produce any significant improvement of the hepatic glutathione system.

4. In conclusion, cirrhosis induction in rats by CCl4 administration produced a decrease in the hepatic glutathione anti‐ oxidant system that was related to an increase in free radical production. Furthermore, zinc supplementation produced a reduction in the degree of hepatic injury and a normalization of lipid peroxidation, but not an improvement of the hepatic GSH anti‐oxidant system.
Capillary Network Patterning During Angiogenesis
Authors: Hansen‐Smith Fay M
Published: March 2003

1. Although much is known of signalling events associated with angiogenesis, starting with a sprout, less is known of how an intact microvascular network is correctly formed following the initiation of sprouting. The aim of the present report is to evaluate some of the factors that could be involved in directing the patterning of the resulting microvascular bed.

2. Hypothetical ‘patterning rules’ are discussed and considered in the context of data obtained from studies of angiogenesis. The guidelines suggest that both tissue‐ and stimulus‐specific regulators are involved in directing patterning.

3. Examples of ‘patterned’ and ‘non‐patterned’ angiogenesis in rat mesentery are given, with evidence to support stimulus‐related differences in angiogenesis patterns.

4. Skeletal muscle angiogenesis follows metabolic patterns within the muscle, as discerned through traditional histochemical evaluation. However, further examination, using confocal microscopy and new patterning assays, indicates that branching patterns differ according to stimulus. Patterning guidelines within the tissue may be important in preventing the growth of sinusoidal vessels.

5. The concept of ‘angiotypes’ is proposed to direct future studies towards understanding how therapeutic angiogenesis or angiostasis applications can be used to obtain correctly patterned microvascular networks. Angiogenesis via ‘branching’ compared with ‘non‐branching’ angiotypes will involve different signalling pathways. Both sprouting and dividing of capillaries are found in the ‘branching’ angiotype, with each pattern having several subtypes that would be expected to be mediated via different signalling mechanisms.
Effect Of Temperature On Responses Of Dog Isolated Lingual And Mesenteric Arteries To Vasoactive Substances
Authors: Tsukada Miyoko , Chiba Shigetoshi
Published: March 2003

1. The effects of temperature on submaximal vasoconstriction to an intraluminal administration of noradrenaline (NA), phenylephrine, tyramine and KCl were investigated in canine isolated and perfused lingual and mesenteric arteries, using the cannula‐inserting method.

2. In lingual arteries, cooling (from 37 to 27°C) caused significant depression of vasoconstriction to the four vasoactive substances used. Rewarming (to 37°C) induced a significant augmentation of constriction by NA, phenylephrine and KCl, but not tyramine.

3. In mesenteric arteries, cooling depressed tyramine‐ and KCl‐induced constrictions, but had no effect on NA‐ and phenylephrine‐induced vasoconstriction. Only in the case of KCl‐induced constrictions did rewarming induce a potentiation of the vasoconstrictor response.

4. We conclude that: (i) cooling induces a depression of voltage‐dependent Ca2+ channels and rewarming may induce a potentiation of Ca2+ channels in both arteries; (ii) α1‐ adrenoceptor‐operated Ca2+ channels are depressed by cooling in lingual arteries but not in mesenteric arteries; and (iii) cooling may induce an attenuation of the re‐uptake function in sympathetic nerve terminals in both arteries and this attenuation may be not rapidly restored by acute rewarming.
Effects Of Tachykinins On Uterine Smooth Muscle
Authors: Patak EN , Story ME
Published: March 2003

1. Sensory nerves supplying the mammalian uterus have been shown to contain substance P (SP) and neurokinin (NK)A. This review presents some of the advances that have led to a greater understanding of the effects of tachykinins on uterine smooth muscle.

2. The cell‐surface peptidase neprilysin (EC.3 24.11, endopeptidase 24.11, enkephalinase, CALLA, CD10) has been shown to play a major role in regulating the actions of tachykinins on both rat and human myometrium. Because this peptidase is known to be regulated by steroids and pregnancy, its effects may be of physiological relevance.

3. Tachykinins produce contractions of isolated myometrial preparations from non‐pregnant rats and mice. The NK2 receptor mediates these effects in rat uterus, while the NK1 receptor may mediate these effects in the mouse uterus.

4. The effects of tachykinins have been examined on myometrial preparations obtained at Caesarean section from near‐term pregnant women. In the presence of the peptidase inhibitors (thiorphan, captopril and bestatin), the mammalian tachykinins SP, NKA and NKB produced concentration‐dependent uterine contractions.

5. The order of agonist potency NKA > SP = NKB suggested that NK2 receptors mediate uterine contractions in the human. This was confirmed using the stable analogues [Sar
9,Met(O2)
11]SP, [Lys
5MeLeu
9Nle
10]NKA(4–10) and [N‐MePhe
7]NKB, which are NK1, NK2 and NK3 receptor selective, respectively. Only [Lys
5MeLeu
9Nle
10]NKA(4–10) produced concentration‐related contractions of human uterine smooth muscle.

6. The experimental findings described in the present review, taken together with results published previously in the literature, indicate that tachykinin peptides may play a physiological or pathophysiological role in regulating uterine smooth muscle activity. However, more extensive research will be required to confirm such a role for these peptides.
Effect Of Organic Cations On The Renal Tubular Secretion Of Pseudoephedrine In The Rat
Authors: Strindelius Lena C , Nation Roger L , Evans Allan M , Cabot Juanita L , Corbett Kathryn M
Published: March 2003

1. Pseudoephedrine is a weak organic base that undergoes renal tubular secretion. The aim of the present study was to assess whether two other commonly used weak organic bases (cimetidine and morphine) inhibit the renal tubular secretion of pseudoephedrine in the rat isolated perfused kidney.

2. A total of 12 perfusions were performed with four perfusions in each of three treatment groups. In the control group, pseudoephedrine was administered as a bolus dose of [14C]‐pseudoephedrine and unlabelled pseudoephedrine to achieve an initial perfusate concentration of 0.4 μg/mL. For the treatment groups, pseudoephedrine was administered as above and cimetidine or morphine was added to the perfusion medium in increasing concentrations of 0.5–12.5 and 0.2–5.0 μg/mL, respectively.

3. The mean (±SD) fraction unbound of pseudoephedrine alone in perfusate was 0.866±0.014 and was not different (P > 0.05) in the presence of cimetidine or morphine.

4. In control experiments, the renal excretory clearance (CLR) of pseudoephedrine was three‐fold greater than glomerular filtration rate (GFR), yielding a ratio consistently greater than unity, which indicates extensive net tubular secretion of pseudoephedrine. The CLR and total clearance of pseudoephedrine were similar, suggesting an absence of renal metabolism of pseudoephedrine.

5. The CLR/GFR ratio for pseudoephedrine was not affected by morphine, but was significantly reduced (P < 0.05) in the presence of cimetidine.

6. The results indicate that cimetidine inhibits the renal tubular secretion of pseudoephedrine.
Proceedings of the Australian Neuroscience Society Symposium: Schizophrenia A REVIEW OF THE NEUROPATHOLOGY OF SCHIZOPHRENIA
Authors: Halliday Gm
Published: March 2003

1. Research on the structural basis for schizophrenia was considered a graveyard for neuropathologists, largely because its aetiology has remained obscure. However, there have been several recent major reviews and studies in leading journals on the neuropathology of schizophrenia highlighting the alterations found in the brains of schizophrenic patients.

2. It is clear from the evidence that schizophrenia can no longer be considered a purely functional psychosis with no structural basis. Multiple and possibly widespread neural systems are likely to participate, because diffuse ventricular enlargement and decreased cortical volume are common in schizophrenia. Interestingly, these features do not herald neuronal loss, findings similar to those obtained in alcoholic and aged populations. Impairment in judgement is common to all these subject groups.

3. The frontal and temporal lobes and their thalamic relays appear particularly affected in schizophrenia and there is some evidence for significant asymmetries. These regions are also consistently affected in patients with neurodegenerative cognitive impairment, although patients with schizophrenia can be distinguished by a lack of classical tissue pathology.

4. The cellular phenotypes that must be structurally compromised have yet to be definitively identified and the relationship between any neurochemical and structural abnormality remains unclear. The subtlety of these changes and their diffuse nature have evoked a consistent chorus that schizophrenia is a neurodevelopmental abnormality; however, this is hard to prove at a structural level using cross‐sectional post‐mortem analyses.
Proceedings of the Australian Physiological and Pharmacological Society Symposium: The Hypothalamus HYPOTHALAMIC PARAVENTRICULAR NUCLEUS AND CARDIOVASCULAR REGULATION
Authors: Badoer Emilio
Published: March 2003

1. The hypothalamic paraventricular nucleus (PVN) is an important integrative site within the brain composed of magnocellular and parvocellular neurons. It is known to influence sympathetic nerve activity.

2. The parvocellular PVN contains neurons that project to the intermediolateral cell column of the thoraco–lumbar spinal cord (IML). This defines the PVN as an autonomic ‘premotor nucleus’, one of only five present within the brain.

3. Another projection arising from the PVN is a prominent innervation of the pressor region of the rostral ventrolateral medulla (RVLM), also a premotor nucleus. The distribution of the PVN neurons projecting to the RVLM is similar to that of the PVN neurons that project to the IML.

4. It has been found that up to 30% of spinally projecting neurons in the PVN also send collaterals to the RVLM. Thus, there are neurons in the PVN that can: (i) directly influence sympathetic nerve activity (via PVN–IML connections); (ii) indirectly influence sympathetic nerve activity (via PVN–RVLM connections); and (iii) both directly and indirectly influence sympathetic nerve activity (via neurons with collaterals to the IML and RVLM).

5. In the rat, results of studies using the protein Fos to identify activated neurons in the brain suggest that neurons in the PVN with projections to the IML or RVLM may be activated by decreases in blood volume.

6. In conclusion, the PVN can influence sympathetic nerve activity. Within the PVN are neurons with anatomical connections that enable them to affect sympathetic nerve activity either directly, indirectly or via both mechanisms (via collaterals). Studies that have examined the role of specific subgroups within the PVN suggest that PVN neurons with connections to the IML or to the RVLM may play a role in the reflex changes in sympathetic nerve activity that are involved in blood volume regulation.
Proceedings of the Australian Physiological and Pharmacological Society Symposium: New Frontiers in Muscle Research ‘Current’ advances in mechanically skinned skeletal muscle fibres
Authors: Posterino Giuseppe S
Published: March 2003

1. In skeletal muscle, excitation–contraction (E‐C) coupling describes a cascade of cellular events initiated by an action potential (AP) at the surface membrane that ultimately results in muscle contraction. Being able to specifically manipulate the many processes that constitute E‐C coupling, as well as the many factors that modulate these processes, has proven challenging.

2. One of the simplest methods of gaining access to the intracellular environment of the muscle fibre is to physically remove (mechanically skin) the surface membrane. In doing so, the myoplasmic environment is opened to external manipulation.

3. Surprisingly, even though the surface membrane is absent, it is still possible to activate both twitch and tetanic force responses in a mechanically skinned muscle fibre by generating an AP in the transverse tubular system. This proves that all the key steps in E‐C coupling are retained in this preparation.

4. By using this technique, it is now possible to easily manipulate the myoplasmic environment and observe how altering individual factors affects the normal E‐C coupling sequence. The effect of important factors, such as the redox state of the cell, parvalbumin and the sarcoplasmic reticulum Ca2+‐ATPase, on twitch and tetanic force can now be specifically investigated independent of other factors.
Local Pulse Pressure Is A Major Determinant Of Large Artery Remodelling
Authors: Laurent Stéphane , Tropeano Anne‐Isabelle , Lillo‐Lelouet Agnès , Jondeau Guillaume , Laloux Brigitte , Boutouyrie Pierre
Published: March 2003

1. The aim of the present brief review is to show that the pulsatile component of blood pressure is a stronger determinant of large artery remodelling than the steady component (i.e. mean blood pressure).

2. Pulse pressure, which is a strong determinant of cardiovascular events, including coronary heart disease and stroke, is increased when large arteries stiffen. Local pulse pressure, measured with applanation tonometry in normotensives and patients with essential hypertension, explains a significant part of the variance of intima–media thickness at the site of the carotied artery, a proximal elastic artery, whereas mean blood pressure does not contribute. Local pulse pressure has no influence on intima–media thickness at the site of the radial artery, a distal muscular artery that undergoes very little stroke change in diamter.

3. The decrease in carotid pulse pressure is also a major determinant of the regression of catorid intima–media thickness after antihypertensive treatment. Local pulse pressure can influence not only intima–media thickness, but also internal diameter. Indeed, there is a significant association between the lumen enlargement of the ascending aorta in patients with Marfan syndrome and pulse pressure. In addition, carotid pulse pressure is positively correlated with carotid internal diameter in normotensives and hypertensives, and the decrease in carotid internal diameter during long‐term antihypertensive treatment is influenced by the decrease in carotid pulse pressure and not by the reduction in mean blood pressure.

4. We suggest that the effects of pulse pressure on large artery remodelling may explain part of its predictive value on cardiovascular events.
Coronary Dilatation Reserve In Experimental Hypertension And Chronic Heart Failure: Effects Of Blockade Of The Renin–Angiotensin System
Authors: Richer C , Domergue V , Gervais M , Fornes P , Trabold F , Giudicelli J‐F
Published: March 2003

1. The aim of the present study was to investigate left and right ventricular (LV and RV, respectively) coronary vasodilatation reserve (CVR; fluorescent microsphere technique) in rats with hypertension (spontaneously hypertensive rats (SHR)) or congestive heart failure (CHF) and the effects of early and chronic renin–angiotensin system (RAS) blockade thereupon.

2. In adult SHR, both LV and RV CVR were impaired, especially in the non‐hypertrophied RV, the main factor involved being coronary vascular remodelling. Blockade of the RAS normalized both LV and RV CVR, mainly through the prevention of hypertension and suppression of the resulting pericoronary fibrosis.

3. In postischaemic CHF rats, there was an early and severe degradation of LV and RV CVR that developed before any significant vascular remodelling and appeared to be linked to the deterioration of cardiac hypertrophy and haemodynamics. This degradation in CVR further worsened over the longer term due to late‐developing pericoronary fibrosis and endothelial dysfunction. Blockade of the RAS had no early effects on LV and RV CVR, but improved RV CVR over the long term, mainly by limiting RV hypertrophy and by preventing the development of pericoronary fibrosis and coronary endothelial dysfunction.

4. In kallikrein–kinin system‐deficient mice, CVR was not different from that of wild‐type mice, suggesting that this system is not implicated in normal CVR regulation.
Environmental And Genetic Determinants Of Intima–Media Thickness Of The Carotid Artery
Authors: Zannad F , Sass C , Visvikis S
Published: March 2003

1. The aim of the present study was to investigate carotid intima–media thickness (CIMT) in relation to anthropometric, environmental and genetic factors, as well as cholesterol and blood pressure levels.

2. The study sample was composed of 89 families, with no documented cardiovascular disease, consisting of 369 subjects (aged from 10 to 54 years) from the Stanislas cohort.

3. Carotid intima–media thickness was measured by B‐mode ultrasonography. Fifteen genetic markers, including genes involved in lipid metabolism, the regulation of blood pressure, thrombosis, platelet function and endothelial cell adhesion, were studied by multiplex assay.

4. The effects of gender, age, smoking, alcohol, body mass index, cholesterol, blood pressure and genetic factors were studied using ANOVA and bivariate and regression analyses.

5. Segregation analysis was also performed to estimate the contribution of genetic and environmental factors to CIMT variability.

6. Carotid intima–media thickness values were not affected by age or by gender up to 18 years of age. Thereafter, CIMT values increased sharply in men and remained significantly higher than in women.

7. Approximately 30% of CIMT variability was attributable to genetic factors. Associations between CIMT and polymorphisms in the apolipoprotein CIII, cholesteryl ester transfer protein, methylene tetrahydrofolate reductase and fibrinogen genes were observed and explained approximately 20% of CIMT variation in men.

8. In women, none of the studied polymorphisms was associated with CIMT variation.

9. Our study gives new perspectives for understanding CIMT variability in healthy middle‐aged subjects.
Interactions Between Sodium And Angiotensin
Authors: Morgan Trefor
Published: March 2003

1. Increased sodium intake causes decreased formation of angiotensin (Ang) II and increased AngII causes increased Na+ retention.

2. Increased sodium intake and increased AngII causes cardiac hypertrophy, but decreased sodium intake regresses cardiac hypertrophy despite high AngII levels. Likewise, decreased Na+ and blockers of the renin–angiotensin system (RAS) in neonatal rats have similar effects on subsequent blood pressure development.

3. Cardiac hypertrophy due to renal hypertension does not regress when the RAS is blocked and rats are on a high salt intake. Likewise, sodium restriction alone does not cause regression; combination of reduced NaCl intake and RAS blockade is required.

4. High doses of perindopril and losartan in combination cause a syndrome in rats on 0.2% NaCl that leads to profound hypotension, polyuria, renal impairment and involution of the heart and death. This is reversed or prevented by a high (4%) NaCl intake, which also prevents the plasma angiotensinogen depletion that occurs with combined blockade on 0.2% NaCl intake.

5. Intake of NaCl and AngII interact at many levels. It is postulated that there is an important interaction at the cellular level that can explain the above events.
Genetic Influences On Cardiovascular Responses To An Acoustic Startle Stimulus In Rats
Authors: Baudrie Véronique , Laude Dominique , Chaouloff Francis , Elghozi Jean‐Luc
Published: March 2003

1. The aim of the present study was to assess the cardiovascular differences among five inbred rat strains (n = 16 per strain), including spontaneously hypertensive rats (SHR), Wistar Kyoto (WKY) rats, Wistar Furth (WF) rats, Fischer (F344) rats and Lewis (Lew) rats and the usual outbred Wistar (W) rat strain (n = 25).

2. These strains were compared under resting conditions for blood pressure (BP) and heart rate (HR) levels and for their baroreceptor–HR reflex sensitivity. In addition, their responses to an acoustic startle stimulus were measured.

3. A consistent rise in BP was observed among the groups as a result of the noise stimulus. This rise in systolic BP (SBP) averaged (±SEM) 37 ± 2 mmHg in the SHR and 34 ± 4 mmHg in F344 rats, while the response was only 23 ± 3 mmHg in WKY rats. Pulse pressure (PP) was increased following noise in all groups. The delay for the BP response for all groups combined was 1.6 ± 0.1 s.

4. Most animals had minimal HR variations, except F344 rats, responding with a 42 ± 13 b.p.m. decrease 3.0 s after the stimulus (i.e. 1.3 s after the maximal 34 ± 4 mmHg SBP rise).

5. The highest SBP (160 ± 3 mmHg) and diastolic BP (104 ± 3 mmHg) were observed in inbred SHR. Other groups were normotensive. Resting PP was elevated for SHR (56 ± 2 mmHg) compared with the other groups (40 ± 2 mmHg). The highest HR was found in F344 and WF rats, with 389 ± 11 and 372 ± 7 b.p.m., respectively. The lowest HR was observed in SHR and Lewis rats, with 335 ± 7 and 323 ± 7 b.p.m., respectively. The least sensitive baroreflex function was observed in SHR (0.8 ± 0.1 b.p.m./mmHg) compared with the other strains (1.4 ± 0.2 b.p.m./mmHg).

6. The present study confirms the importance of genetic factors on the cardiovascular responses of rats to a noise startle stimulus. Two inbred normotensive rat strains, namely F344 and WKY rats, which exhibit a substantial difference in pressor response to noise, may be used to unravel the mechanisms of sympathetic activation.
The Adenine Nucleotide Translocator: Regulation And Function During Myocardial Development And Hypertrophy
Authors: Portman Michael A
Published: March 2003

1. The present review focuses on the adenine nucleotide translocator (ANT), which facilitates exchange of cytosolic ADP for mitochondrial ATP. This protein serves a central role in regulating cellular oxidative capacity.

2. The ANT, a nuclear‐encoded mitochondrial protein, is developmentally regulated and, thus, accumulates within the mitochondrial membrane during maturation.

3. Accumulation of ANT parallels changes in kinetics of myocardial respiration determined from 31P magnetic resonance spectroscopy studies.

4. Thyroid hormone modulates developmental transitions in ANT content, as well as respiratory control patterns. These transitions are linked to quantitative ANT changes, not to alterations in functionality at individual exchanger sites.

5. Developmental programming for ANT and parallel alterations in oxidative phosphorylation kinetics are relevant to the heart, which exhibits remodelling in response to pathological processes. Maladaptive hearts exhibiting ANT deficits demonstrate ADP‐dependent respiratory kinetics similar to the newborn heart. Thus, ANT deficits and alterations in mitochondrial respiratory function may contribute to the pathogenesis of myocardial remodelling and heart failure.
Gaba In The Control Of Sympathetic Preganglionic Neurons
Authors: Llewellyn‐Smith Ida J
Published: March 2003

1. Amino acid neurotransmitters are critical for controlling the activity of most central neurons, including sympathetic preganglionic neurons (SPN), the spinal cord neurons involved in controlling blood pressure and other autonomic functions.

2. In studies reviewed here, SPN were identified either by retrograde tracing from a peripheral target (superior cervical ganglion or adrenal medulla) or by detection of immunoreactivity for choline acetyltransferase (ChAT), the acetylcholine‐synthesizing enzyme that is a marker for all SPN, in intact or completely transected rat spinal cord.

3. Postembedding immunogold labelling on ultrathin sections was then used to detect GABA and sometimes glutamate in nerve terminals on SPN or near them in the neuropil of the lateral horn.

4. In some cases, the terminals were prelabelled to show an anterograde tracer or immunoreactivity for ChAT or neuropeptide Y.

5. This anatomical work has provided information that is helpful in understanding how SPN are influenced by their GABAergic innervation.

6. Immunogold studies showed that the proportion of input provided by GABAergic terminals varies between different groups of SPN. For some groups, this input may be preferentially targeted to cell bodies.

7. Anterograde tracing demonstrated that supraspinal as well as intraspinal GABAergic neurons innervate SPN and investigations on completely transected cord suggested that supraspinal neurons may provide a surprisingly large proportion of the GABAergic terminals that contact SPN.

8. The double‐labelling studies in which other amino acids, ChAT or neuropeptide Y were localized along with GABA indicate that GABAergic terminals contain other neurochemicals that could modulate the actions of GABA, depending on the complement of receptors that are present pre‐ and post‐synaptically.

9. Taken together, these data indicate that GABAergic transmission to SPN may be much more complicated than suggested by the currently available electrophysiological studies.