bluuebunny/crossref_metadata_2025 huggingface dataset:
Armrest versus vacuum bag immobilization in the treatment of breast cancer by radiation therapy: A randomized comparison
Authors: Graham P , Elomari F , Browne L
Published: March 2003

Thirty patients in randomized sequence were simulated in both an armrest and a vacuum bag immobilization device and also randomized to treatment in one of the two devices. Overall patient comfort significantly favoured the use of the armrest, although both were acceptable. Lung exposed in the tangential beams was less in the vacuum bag device. Supraclavicular skin folding was greater in the vacuum bag, but this is probably related to the angle of arm abduction. Treatment times and stability of the setups were not significantly different. This is a small study piloting a technical comparison and the findings require confirmation in a larger sample.
Meningioangiomatosis
Authors: Scroop Rebecca , Voyvodic Frank , Sage Michael R
Published: March 2003

The imaging findings of a case of meningioangiomatosis with pathologic correlation are presented.
Reach for the phone: Urgent imaging findings in obstetrics and gynaecology
Authors: Furness Margaret , Hayward Tina
Published: March 2003

Some imaging findings indicate that a patient is at risk, and are too urgent or too important for the radiologist to rely on written communication alone. Some examples in obstetrics and gynaecology are demonstrated.
Giant cell tumour of the tendon sheath of the hand: A pictorial essay
Authors: Peh Wilfred CG , Wong Yik , Shek Tony WH , Ip Wing‐Yuk
Published: March 2003

Giant cell tumour of the tendon sheath is a soft tissue mass found occasionally in the hand. Its diagnosis can be readily made preoperatively if the characteristic MRI features are appreciated. This pictorial essay demonstrates and describes the imaging findings correlated with histopathological findings in a group of patients with proven giant cell tumour of the tendon sheath.
Lace‐like enhancement pattern of osteosarcoma of rib and liver metastasis in CT scans
Authors: Chan Helen HL , Chan John KF , Ng Wai‐Man , Shek Tony WH , Chan Fu‐Luk
Published: March 2003

The rib is an uncommon site of osteosarcoma. With the use of adjuvant chemotherapy and aggressive surgical resection of the metastatic pulmonary lesions, extrapulmonary metastases are becoming more clinically evident. Primary rib osteosarcoma with extrapulmonary metastasis is exceedingly rare. A case is reported, showing that the pattern of metastasis of rib osteosarcoma is similar to that of primary bone osteosarcoma. The liver metastasis occurred after resection of the metastatic pulmonary lesions. A CT scan of the primary rib lesion and liver metastasis both showed a lace‐like enhancement pattern, its histological appearance corresponding with neoplastic osteoid. With the increasing use of CT abdomen for localization of extrapulmonary metastases, lace‐like enhancement may be seen more readily in the future.
Tandem lesions of the carotid circulation: Combined extracranial endarterectomy and intracranial transluminal angioplasty
Authors: Gock Stephen L , Mitchell Peter J , Field Peter L , Atkinson Noel , Thomson Kenneth R
Published: March 2003

A case series is presented demonstrating a unique approach to the treatment of tandem atherosclerotic lesions of the internal carotid artery. Between 1994 and 1999 eight patients with tandem lesions of the internal carotid artery were treated by combined carotid endarterectomy for the proximal lesion and intraoperative angioplasty of the distal intracranial lesion via the carotid arteriotomy. The success and complication rates were evaluated. A 100% technical success rate was achieved with one post procedural complication by ipsilateral stroke within 24 h. The advantages of this technique include the treatment of tandem lesions by the one procedure, improved transluminal access to the intracranial lesion and the ability to reduce the risk of embolism by flow control during balloon inflation.
Focal myositis
Authors: Galloway Howard R , Dahlstrom Jane E , Bennett Genevieve M
Published: March 2003

Focal myositis is a rare, benign focal inflammation of muscle. The lesion often presents as a mass that may be mistaken for a soft tissue sarcoma. This report describes the MRI and histopathological features of a case and illustrates how the diagnosis may be suspected on the basis of the MR findings.
Fetus in fetu. Rare cause of a lump in an adult’s abdomen
Authors: Awasthi M , Narlawar R , Hira P , Shah P
Published: March 2003

Fetus in fetu is a rare entity. The patient usually presents in childhood. A case in which the patient presented in adulthood, with a lump in the abdomen, is reported. Computed tomography findings were diagnostic of this condition and a prospective diagnosis could be made. Computed tomography also helped to differentiate it from mature teratoma.
Comparison of lung scintigraphy and CT angiography in the diagnosis of pulmonary embolism
Authors: Chen Suet‐Wan , Mouratidis Bill
Published: March 2003

In our institution, as in others, pulmonary angiography is not used in the diagnosis of pulmonary embolism because of its perceived risks. We compared the results on lung scintigraphy and computed tomography angiography (CTA) in 116 consecutive patients with suspected pulmonary embolism. In 14 patients with normal lung scans 13 (93%) were also normal with CTA. In the 73 patients with low probability lung scans only five (7%) demonstrated pulmonary embolism with CTA. In 12 patients with high probability lung scans 11 (92%) demonstrated pulmonary embolism on CTA. However, in the 17 patients with intermediate probability lung scans, 10 (58.8%) showed embolism with CTA. We conclude that wherever practicable lung scans should be performed in all patients due to its relatively low radiation burden and that CTA be performed in patients with intermediate probability scans due to the high incidence of pulmonary embolism. Patients with either a normal scan or high probability scan should be treated appropriately. In patients with low probability scans CTA should be performed in those with a high clinical suspicion of thromboembolism.
Renal involvement in multifocal osteosarcoma
Authors: Karabulut Nevzat , Ariyürek O Macit , Gülsün Meltem , Akyüz Canan
Published: March 2003

A rare case of multifocal osteosarcoma metastatic to kidney, lung and lymph nodes is presented. Radiological findings included multiple foci of sclerotic lesions involving the axial and peripheral skeleton, a heterogeneous renal mass with areas of calcification, multiple pulmonary metastases with pneumothorax, and partially calcified enlarged mediastinal and abdominal lymph nodes.
Mycosis fungoides involving the oral cavity
Authors: Chua Margaret S‐T , Veness Michael J
Published: March 2003

Mycosis fungoides is a malignant T‐cell lymphoproliferative disease with a predilection for cutaneous involvement. Extracutaneous disease is uncommon and oral mucosal involvement is rare. We describe a case of mycosis fungoides involving the hard palate treated with radiotherapy. The relevant literature on this topic is reviewed.
Management preferences following radical inguinal orchidectomy for Stage I testicular seminoma in Australasia
Authors: Hruby G , Choo R , Jackson M , Warde P , Sandler H
Published: March 2003

A survey to evaluate the preferred patterns of management of Stage I seminoma was conducted during March 2001. The questionnaire was distributed by the Royal Australian and New Zealand College of Radiologists to all qualified radiation oncologists, 74 out of 170 responded. All performed a staging CT scan of the abdomen and pelvis. Thoracic imaging consisted of either chest X‐ray (29%) or chest CT (38%) while 33% performed both. Fifty‐four percent of radiation oncologists discussed surveillance with their patients but estimated that 5% or less would choose this option. The most commonly prescribed dose was 25 Gy in 15 or 20 fractions (79%). Sixty‐five percent of respondents treated the para‐aortic (PA) nodes alone. Forty‐two of 48 clinicians treating the PA field reported a change in practice after publication of the Medical Research Council study in 1999. Of these, 40 and 23% perform CT scans of the pelvis annually and every 6 months. Thirty‐one percent did no follow‐up CT scan. Compared to a similar survey from North America, we are more likely to use PA fields and less likely to discuss surveillance. As in the USA, and in contrast to Canada, few patients choose surveillance. There is no consensus regarding the frequency of follow‐up scans in either North America or Australasia.
Magnetic resonance imaging findings in an unusual case of atlanto axial dislocation and vertebral artery–vein fistulas in a patient of neurofibromatosis‐1
Authors: Maheshwari Sharad , Kale Hrishikesh A , Desai Shrinivas B , Kohli Anirudh
Published: March 2003

Vertebral arteriovenous fistulas are uncommon in neurofibromatosis. We describe MRI findings of a patient with an unusual association of bilateral vertebral arteriovenous fistulas with an atlantoaxial dislocation in the setting of neurofibromatosis.
Tuberous sclerosis: A presentation of less‐commonly encountered stigmata
Authors: Morris BS , Garg A , Jadhav PJ
Published: March 2003

The protean manifestations of the tuberous sclerosis complex have lent this condition to extensive review in textbooks and in the medical literature. This condition generally presents by virtue of its neurological manifestations. Osseous stigmata, when encountered, are generally asymptomatic and do not require specific treatment owing to their benignity. We present the case of a young man with a slowly enlarging facial swelling for whom cosmetic surgery was considered. The swelling, present since childhood, had in time assumed disfiguring proportions. In what was hitherto considered an isolated facial deformity, a skull radiograph followed by CT revealed neurological stigmata of tuberous sclerosis. A large cerebellar hamartoma, proliferative soft tissue in the scalp adjacent to focal hyperostosis of the calvarium and the accompanying hemifacial changes seen in this patient constitute less commonly described features of tuberous sclerosis.
Abnormal uptake of Technetium‐99 m hydroxymethylene diphosphonate in the liver
Authors: Roman Marcin R , Larcos George , Angelides Socrates , Devadas Michael
Published: March 2003

Diffuse liver uptake on bone scintigraphy is a rare occurrence with only a few reports in the literature. A case of diffusely increased uptake in a patient with acute hepatitis is presented.
MRI in kernicterus
Authors: Shah Zarine , Chawla Ashish , Patkar Deepak , Pungaonkar Sona
Published: March 2003

Kernicterus (bilirubin encephalopathy) is a disease entity with a very high rate of mortality in neonates. The children who survive are left with neurological deficits such as choreoathetosis, sensorineural deafness and mental retardation. Magnetic resonance imaging of the brain in this condition has specfic findings which aid in the accurate diagnosis of the condition, along with clinical and biochemical criteria. Reports have shown involvement of the globus pallidus, putamen, and less commonly the thalamus. More specific involvement may be isolated lesions of the globus pallidus. Magnetic resonance imaging has shown a good sensitivity in this condition.
Coexistent gallbladder carcinoma in Mirizzi syndrome
Authors: Chiam Quee Li , Lau Kenneth
Published: March 2003

A 52‐year‐old woman presented with right upper quadrant pain and obstructive jaundice. Computed tomographic scan showed Mirizzi syndrome type 1 and a thickened and calcified gallbladder wall, raising the possibility of coexistent gallbladder carcinoma that was later confirmed on histology post‐cholecystectomy.
Why a breast boost should remain a controversial aspect of routine breast conservation management in Australia and New Zealand in 2002
Authors: Graham P , Capp A , Fox C , Nasser E , Delaney G , Ahern V , Wratten C
Published: March 2003

Two randomized trials have recently shown a statistically significant improvement in local control when a boost is employed in the conservative treatment of early breast cancer. However, unresolved issues of cost effectiveness, potentially increased toxicity and the inability to automatically generalize these results to Australian and New Zealand practice remain. In view of these unresolved controversies, the St George and Wollongong hospitals breast boost trial (SGW trial) will continue to recruit.
Renal colic: A prospective evaluation of non‐enhanced spiral CT versus intravenous pyelography
Authors: Mendelson Richard M , Arnold‐Reed Diane E , Kuan Melvyn , Wedderburn Andrew W , Anderson James E , Sweetman Gregory , Bulsara Max K , Mander Julian
Published: March 2003

The aim of this study was to compare non‐enhanced spiral CT (NECT) and intravenous pyelography (IVP) in patients with suspected acute renal colic. Two‐hundred patients presenting to the Emergency Department with suspected acute renal colic were randomized into groups undergoing NECT or IVP. The main outcome measures were diagnostic utility, incidence of alternative diagnoses, requirement for further imaging, length of hospital stay, urological intervention rates, radiation dosage and costs. Non‐enhanced spiral CT was better than IVP in making a definitive diagnosis of ureteric calculus or of recent calculus passage (65/102 or 66% vs 42/98 or 41%; P = 0.003). Calculi were missed in two patients in the IVP group. Two patients in each group had alternative diagnoses by initial imaging. There was no difference in the length of hospital stay or intervention rate. More plain X‐rays during admission and more IVPs during follow up were performed in the NECT group. Effective radiation dosages were 2.97 mSv (IVP) and up to 5 mSv (NECT). Non‐enhanced spiral CT provided greater diagnostic utility in this randomized comparison but no difference in measured outcomes. The incidence of alternative diagnoses was low, probably due to patient selection. Financial costs for each modality are comparable in a public tertiary hospital. Radiation dosages are higher for NECT and, for this reason, it might be appropriate to consider limiting NECT use to patients who have do not have classical symptoms of renal colic, to older patients and those with a contraindication to the administration of intravenous contrast media.
GENDER DIFFERENCES AND ENDOTHELIUM‐ AND PLATELET‐DERIVED FACTORS IN THE CORONARY CIRCULATION
Authors: Miller Virginia M , Lewis Debra A , Barber Dustan A
Published: March 2003

1. Experiments were designed to determine whether or not interactions of platelets with coronary arteries are affected by gender or oestrogen‐status.

2. Platelets and right coronary arteries were isolated from sexually mature male, female and ovariectomized pigs. Arteries were suspended in organ chambers for the measurement of isometric force. Responses of rings, with and without endothelium, were evaluated to aggregating platelets and the platelet products 5‐hydroxytryptamine (5‐HT) and adenosine diphosphate (ADP).

3. Release of 5‐HT, thromboxane A2 (TXA2) and prostacyclin were measured from platelets.

4. Platelets caused relaxations of rings with endothelium from all pigs. However, in rings without endothelium, consistent contractions were observed only in rings from male pigs.

5. The release of 5‐HT and prostacyclin was greatest from platelets of ovariectomized pigs compared with male and female pigs. Release of TXA2 was greatest from platelets of male pigs.

6. Endothelium‐dependent relaxations to ADP and contractions to 5‐HT were similar among the three groups.

7. These results suggest that there may be gender‐specific differences in vasomotor responses to autogenous platelets but not to the platelet‐derived products 5‐HT and ADP. Furthermore, there are gender differences in platelets in the release of cyclo‐oxygenase metabolites of arachidonic acid and 5‐HT. These products could contribute to gender differences in response to injury in the coronary circulation.
EFFECT OF PHOSPHORYLATION ON L‐TYPE CALCIUM CURRENT IN VENTRICULAR MYOCYTES DIALYSED WITH PROTEOLYTIC ENZYMES
Authors: Dooley PC , Hancox JC , Chapman RA
Published: March 2003

1. L‐Type Ca2+ channels play important roles in cardiac excitation and conduction. The present study used the whole‐cell patch‐clamp technique to investigate properties of Ca2+ channels in guinea‐pig isolated ventricular myocytes. The effects of internal application of the proteolytic enzymes trypsin and carboxypeptidase (CBP) on the whole‐cell L‐type Ca2+ current (ICa) were determined. When the effects of the enzymes on ICa had reached steady state, the effects of isoprenaline (ISP) or 2,3‐butane‐dione monoxime (BDM), which increase and decrease channel phosphorylation, respectively, were examined. The effects of these agents were compared with those observed in the absence of enzyme pretreatment.

2. The amplitude and inactivation characteristics of ICa during depolarizing voltage‐clamp commands to +10 mV (0.1 Hz) were determined at 37°C.

3. Trypsin and CBP (both at concentrations of 1 mg/mL in the pipette solution) increased the amplitude of ICa 4.2‐ and 2.8‐fold, respectively, and each enzyme increased the time constant of the slowly inactivating current by 50%.

4. Trypsin decreased the potential at which ICa was half maximally activated from (mean±SD) −1.4±2.2 mV (n = 9) to −11.3±2.5 mV (n = 7). Although CBP increased ICa amplitude, it did not shift the half‐maximal activation voltage. Maximum conductance was increased 5.3‐fold by trypsin and 2.2‐fold by CBP.

5. Isoprenaline (1 μmol/L) had no effects in myocytes dialysed with trypsin, but significantly increased the current in myocytes dialysed with CBP by 8%.

6. At 12 mmol/L, BDM had no effect on current amplitude in the presence of trypsin, but decreased the time constant of slow inactivation to control values. After dialysis with CBP, BDM significantly decreased the maximum current by 11% and also decreased the rate of slow inactivation towards control values.

7. These data suggest that trypsin and CBP may have digested a part of the calcium channel that normally restricts current flow, but to different extents. The enzymes interacted with BDM and ISP in a fashion suggesting that two sites may influence the amplitude of the current and at least two other sites may influence the time course of the slowly inactivating current.
PULMONARY INFLAMMATION WITHOUT BRONCHIAL HYPERRESPONSIVENESS IN VIVO OR IN VITRO AFTER SEPHADEX INSTILLATION IN PIGS
Authors: McFawn PK , Gray PR , Thomas J , Mitchell HW
Published: March 2003

1. In rodent models, Sephadex produces pulmonary inflammation that may be associated with bronchial hyperresponsiveness. In the present study we examined whether Sephadex‐induced inflammation altered airway narrowing in pigs.

2. Twenty millilitres of 10 mg/mL Sephadex suspension was instilled twice intratracheally into anaesthetized pigs (days 1 and 7 of a 9 day study). In vivo bronchial responsiveness was assessed from the effect of acetylcholine (ACh) aerosol on airways resistance and dynamic compliance before Sephadex instillation and on days 3, 5 and 9. Lung histology and in vitro bronchial responsiveness was assessed on day 9. In vitro responsiveness was assessed by measuring the reduction in flow through perfused 2 mm i.d. bronchial segments in response to ACh applied luminally and adventitially.

3. Sephadex produced a focal peribronchial granulomatous reaction characterized by the presence of macrophages, eosinophils, neutrophils and giant cells. Changes in airway resistance and lung compliance in response to ACh did not change over the study period. The response of perfused bronchial segments to luminally or adventitially applied ACh was also unaltered.

4. Sephadex‐induced pulmonary inflammation does not alter airway narrowing in vitro nor bronchial hyperresponsiveness in vivo in the pig.
REGULATION OF VASCULAR TONE BY ENDOTHELIUM‐DERIVED HYPERPOLARIZING FACTOR
Authors: Cheung DW , MacKay G Chen, MJ , Burnette E
Published: March 2003

1. Endothelium‐derived hyperpolarizing factor (EDHF) mediates the nitric oxide (NO)‐independent component of the relaxation in rat mesenteric arteries. The relationship between hyperpolarization and vascular tone was studied by simultaneous recording of membrane potential with intracellular microelectrodes and tension in ring segments of rat mesenteric arteries.

2. By depolarizing arteries with high potassium solutions, it was determined that the threshold for contraction is approximately −46 mV. Maximum contraction was attained when the arteries were depolarized to −20 mV. Thus, 1 mV depolarization resulted in an approximate 4% increase in tone. This relationship was not altered in spontaneously hypertensive rats.

3. Noradrenaline (0.3 μmol/L) caused contraction and depolarized arteries by 13 mV. Acetylcholine caused endothelium‐dependent relaxation and hyperpolarization up to 14 mV. In the presence of Nω‐nitro‐L‐arginine, the EDHF‐mediated relaxation was correlated to hyperpolarization. A hyperpolarization of 1 mV corresponded to a 4.3% decrease of the induced tone.

4. At concentrations (10 μmol/L) causing total relaxation, the maximum hyperpolarization induced by NO was only 7.6 mV.

5. A maximum relaxation of 88% was observed with pinacidil (3 μmol/L), despite a 25 mV hyperpolarization. Relaxations to NO and pinacidil were not correlated with hyperpolarization. At similar levels of hyperpolarization, NO and pinacidil elicited more relaxation than EDHF.

6. These studies show that vascular tone is very sensitive to membrane potential change in the range between −46 and −20 mV in the rat mesenteric artery. The relaxation response to EDHF, unlike that to NO and pinacidil, can be accounted for solely by its effect on the membrane potential.
ENDOMETRIAL ENDOTHELIN: REGULATOR OF UTERINE BLEEDING AND ENDOMETRIAL REPAIR
Authors: Salamonsen Lois A , Marsh Marion M , Findlay Jock K
Published: March 2003

1. Endothelin (ET) and its mRNA are present in endometrium. Expression of ET varies across the menstrual cycle, reaching maximal levels in the premenstrual phase, suggesting a paracrine role in endometrial bleeding and/or repair.

2. The major cellular source of ET is the epithelium, although endothelium and decidualized stroma are additional sites of production. Epithelial ET is the ET‐1 isoform and this is able to contract rat thoracic aortic rings ex vivo.

3. Endothelin‐1 production by cultured endometrial epithelial cells is markedly increased by serum and, to a lesser extent, by transforming growth factor‐β and interleukin‐1α, but not by epidermal growth factor, oxytocin, arginine vasopressin, thrombin or angiotensin II, which stimulate ET production in other tissues.

4. Endothelin‐1 has mitogenic actions on endometrial stromal cells; it stimulates the uptake of [3H]‐thymidine, acting via the AP‐1 cis element c‐jun.

5. Neutral endopeptidase (NEP), a membrane‐bound ectoenzyme that is capable of degrading ET, is localized principally in endometrial stroma and immunoreactivity is maximal in the secretory phase of the cycle.

6. A potential role for ET in regulating endometrial bleeding is suggested by studies on endometrium from two groups of women who were experiencing abnormal uterine bleeding: users of the contraceptive Norplant® (Leiras Co., Turku, Finland) and subjects with documented menorrhagia. In both groups, ET‐1 immunoreactivity in endometrial epithelium was markedly reduced compared with the normal menstrual cycle and did not vary cyclically, while NEP immunoreactivity, particularly in the epithelium, was increased. Thus, ET may be involved in endometrial bleeding, as a vasoconstrictor before the onset of menstruation when vasoconstriction is intense and, subsequently, when it may be required in the cessation of menstrual bleeding. Furthermore, the mitogenic actions of ET may play a role in endometrial regeneration and remodelling during the menstrual cycle, particularly following menstruation.
DIFFERENT RESPONSES TO SURGICAL STRESS BETWEEN EXTRA DOMAIN A+ AND PLASMA FIBRONECTINS
Authors: Satoi Sohei , Hiramatsu Yoshifumi , Kitade Hiroaki , Kwon A‐Hon , Matsui Kosuke , Miyashita Keiichi , Sakashita Eiji , Sekiguchi Kiyotoshi , Takahashi Hakuo , Kamiyama Yasuo
Published: March 2003

1. Fibronectins (FN) are believed to have a role in haemorheological perturbation associated with tissue damage. Fibronectins exist in two antigenically related forms, plasma (p) and cellular fibronectin, which has the extra domain sequences A (EDA) or B (EDB). The present study was designed to determine changes in plasma p‐FN and EDA + FN under different types of surgical stress.

2. Sixty‐two patients were divided into three groups: (i) group A, 33 patients undergoing hepato–pancreato–biliary surgery; (ii) group B, 19 patients undergoing laparoscopic cholecystectomy; and (iii) group C, 10 patients with postoperative complications. Plasma FN and EDA + FN levels were measured in these patients undergoing different types of surgical operation and either with or without liver cirrhosis using an enzyme‐linked immunosorbent assay.

3. After surgery, a significant decrease in p‐FN levels and a significant increase in EDA + FN levels was observed in all patient groups compared with pre‐operative levels. The duration of increased EDA + FN levels, but not p‐FN levels, in group A patients was significantly longer than in group B patients. Although changes in p‐FN levels between patients with and without liver cirrhosis were significantly different, there were no significant differences in the EDA + FN levels between these two patient groups.

4. In conclusion, EDA + FN and p‐FN levels were found to exhibit opposite responses to surgical stress. Furthermore, with greater surgical stress, greater increases in EDA + FN levels were seen. The presence of liver cirrhosis had no significant effect on EDA + FN levels during the perioperative period; however, p‐FN levels were significantly affected.

5. Thus, it is suggested that plasma EDA + FN levels reflect the magnitude of surgical stress more closely than do p‐FN levels.
EFFECTS OF HYPOXIC EXERCISE CONDITIONING ON WORK CAPACITY, LACTATE, HYPOXANTHINE AND HORMONAL FACTORS IN MEN
Authors: Mori Masatake , Kinugawa Toru , Endo Akihiro , Kato Masahiko , Kato Tatsuo , Osaki Shuichi , Ogino Kazuhide , Igawa Osamu , Hisatome Ichiro , Ueda Mayumi , Miura Noritoyo , Ishibe Yuichi , Shigemasa Chiaki
Published: March 2003

1. Hypoxanthine is a purine degradation product and exercise plasma hypoxanthine can be an index of ATP supply–demand imbalance during exercise. The present study determined the effects of hypoxic exercise conditioning on work capacity, blood lactate, plasma hypoxanthine and various neurohormonal factors.

2. Blood lactate, plasma hypoxanthine and neurohormonal factors (catecholamines, renin–angiotensin system activity and natriuretic peptides) were measured at rest and after maximal cardiopulmonary exercise testing (at sea level) both at pre‐ and post‐hypoxic exercise conditioning in six males (40±2 years). The training protocol consisted of ergometer exercise twice weekly for 40 min in a hypobaric chamber (61.7–47.2 kPa) for 3 weeks.

3. Pulmonary function and haematological and echocardiographic parameters were not altered after hypoxic exercise conditioning. Work rate at peak exercise (264±10 vs 321±31 W; P = 0.10) tended to be increased and peak O2 pulse (15.0±1.0 vs 18.4±1.4 mL/beat; P < 0.05) increased after exercise conditioning. The double product during submaximal exercise decreased and systolic blood pressure at peak exercise increased after exercise conditioning. Resting and exercise neurohormonal factors were unchanged, except for reduced resting plasma adrenaline levels. Blood lactate at peak exercise (7.4±0.7 vs 4.8±0.5 mmol/L; P < 0.05) became lower and peak plasma hypoxanthine (43.2±5.7 vs 26.4±5.0 μmol/L; P < 0.1) tended to be decreased after exercise conditioning.

4. Hypoxic exercise conditioning tended to increase maximal power output with a decrease in exercise blood lactate and a trend towards a decrease in exercise plasma hypoxanthine. These data suggest that exercise conditioning under simulated altitude may improve ATP supply–demand imbalance during exercise with less anaerobiosis, which could contribute to enhanced endurance performance.
EFFECT OF HYPERINSULINAEMIA ON RENAL FUNCTION AND NITRATE/NITRITE EXCRETION IN HEALTHY SUBJECTS*
Authors: Komers Radko , Pelikanová Terezie , Kazdová Ludmila
Published: March 2003

1. In addition to its metabolic actions, insulin acts as a vasodilator in certain vascular beds, such as skeletal muscle. It has been shown that this effect is mediated by endothelium‐derived nitric oxide (NO). Unlike in the skeletal muscle, insulin–NO interactions in the kidney, another major site of insulin action, have been less studied. The aim of the present study was to explore the role of NO in renal effects of hyperinsulinaemia in healthy subjects.

2. Changes in renal function and urinary nitrate/nitrite (NO2−/NO3−; Griess method) levels as a marker of renal production of NO were assessed during euglycaemic hyperinsulinaemic clamp and compared with normoinsulinaemic isovolaemic conditions (administration of the same amount of insulin/glucose‐free vehicle) in 10 healthy male volunteers.

3. Hyperinsulinaemia was associated with a decrease in renal excretion of stable metabolites of NO (mean (±SEM) 0.56±0.12 vs 0.38±0.05 μmol/min, respectively; P < 0.05). In contrast, administration of the same volume of insulin‐free vehicle resulted in elevation of urinary NO2−/NO3− (P < 0.05). The changes in renal sodium handling followed a similar pattern as changes in the renal excretion of NO2−/NO3− with a significantly different response to hyperinsulinaemia when compared with normoinsulinaemia (F = 12.2; P < 0.001). The mean arterial pressure, blood levels of low‐density lipoprotein–cholesterol and free fatty acids, possible factors influencing renal and systemic NO production, remained constant throughout both experiments.

4. These results suggest that hyperinsulinaemia is associated, in healthy males, with a decrease in renal generation of NO. In contrast, mild volume expansion with insulin‐free vehicle resulted in increased excretion of NO metabolites. This insulin‐induced attenuation of renal NO synthesis may contribute to the anti‐natriuretic actions of insulin.
ROLE OF NITRIC OXIDE AND ENDOTHELIUM IN THE FLOW‐INDUCED DILATION OF RAT CORONARY ARTERIES UNDER TWO PRECONSTRICTION CONDITIONS
Authors: Véquaud Philippe , Pourageaud Fabrice , Freslon Jean‐Louis
Published: March 2003

1. Pressure‐induced tone and flow‐induced dilations were studied in a rat perfused epicardial coronary artery mounted in an arteriograph. Spontaneous tone was assessed in arteries submitted either to 60 or 90 mmHg intraluminal pressure either under control conditions, after incubation with NG‐nitro‐L‐arginine methyl ester (L‐NAME; 100 μmol/L) or after endothelial denudation. Flow‐induced dilation was quantified under these conditions in preparations either submitted to 60 mmHg and preconstricted with 10 μmol/L 5‐hydroxytryptamine (5‐HT) or exhibiting spontaneous tone at 90 mmHg.

2. Spontaneous tone was greater at 90 mmHg compared with tone obtained at 60 mmHg (21±2 vs 10±2% reduction of the fully dilated diameter after sodium nitroprusside incubation, respectively). Incubation with L‐NAME or removal of the endothelium significantly increased spontaneous tone at both pressures compared with control.

3. In arteries submitted to 60 mmHg and preconstricted with 10 μmol/L 5‐HT, flow (0–800 μL/min) induced a continuous dilation (maximal value 63±4%). As a function of flow, shear stress first increased and then plateaued at values of approximately 76±6 dyn/cm2. After L‐NAME incubation or endothelial denudation, the flow‐induced dilation was reduced to the same extent and was obtained for higher values of shear stress (172±14 and 150±14 dyn/cm2, respectively).

4. In arteries exhibiting spontaneous tone, starting flow led, first, to a constriction followed by a dilation up to 76±4% of the initial tone. Incubation with L‐NAME greatly altered flow‐ induced dilation. Endothelium removal further reduced the dilation obtained for very high values of shear stress (up to 300 dyn/cm2).

5. The present study shows that different patterns of vasodilation induced by flow can be observed, depending on the initial vasoconstrictor stimulus. In 5‐HT‐preconstricted arteries, flow‐induced dilation appears to be fully dependent on the synthesis and release of nitric oxide. In arteries with spontaneous tone, a vasoconstrictor substance could be released for low values of flow. Nitric oxide is mainly, but not exclusively, responsible for the vasodilation. For both experimental conditions, removal of the endothelium greatly reduced the response, but a dilation was still observed.
HYPERGLYCAEMIA ABOLISHES THE ANTIHYPERTROPHIC EFFICACY OF BRADYKININ IN RAT VENTRICULAR MYOCYTES
Authors: Dusting Ac Rosenkranz, Gj , Ritchie Rh
Published: March 2003

1. Bradykinin inhibits hypertrophy of rat ventricular myocytes, but only in the presence of endothelial cells.

2. The influence of hyperglycaemia on the ability of bradykinin to prevent hypertrophy was investigated in adult rat ventricular myocytes cocultured with bovine aortic endothelial cells (BAEC).

3. In myocytes cocultured with normal BAEC, angiotensin II (AngII; 1 μmol/L) significantly increased [3H]‐phenylalanine incorporation (an in vitro marker of hypertrophy) by 32±2%. This was abolished by bradykinin (10 μmol/L).

4. Pretreatment of BAEC with high glucose (25 mmol/L for 24 h) prior to coculture with myocytes reduced the antihypertrophic effect of bradykinin, but did not modulate the hypertrophic effect of AngII.

5. Pretreatment of BAEC with hyperglycaemia abolishes the antihypertrophic efficacy of bradykinin in rat ventricular myocytes cocultured with BAEC. This has implications for the action of angiotensin‐converting enzyme inhibitors.
IMPLICATION OF HYPERTENSIVE RAT MODELS FOR PRIMORDIAL NUTRITIONAL PREVENTION OF CARDIOVASCULAR DISEASES
Authors: Yamori Yukio
Published: March 2003

1. Various substrains maintained during selective sib‐mating contributed to the establishment of spontaneously hypertensive rats (SHR) with a variety of clinical features.

2. Stroke‐prone SHR (SHRSP), developing haemorrhagic and/or ischaemic stroke spontaneously, are regarded as a model for osteoporosis.

3. The genetic mechanisms of spontaneous hypertension have been attributed pathophysiologically to neural and structural vascular alterations.

4. The mechanisms of stroke are ascribed to the limited regional oxygen and nutrient supplies to the brain areas fed by perforating arteries.

5. The genome‐wide linkage analysis on the F2 obtained by crosses of SHRSP with normotensive strains has demonstrated different gene loci contributing to the development and maintenance of hypertension during the ageing process and also genes influencing the susceptibility to stroke without any effect on blood pressure.

6. Experimental studies in SHRSP revealed that stroke could be prevented by protein, Ca‐ or Mg‐supplemented diets, particularly if given in the early stage, indicating the importance of primordial nutritional prevention of cardiovascular diseases (CVD).

7. Experimental findings in SHRSP as well as epidemiological studies on nutrition and CVD indicate the future avenue towards ‘predictive‐preventive medicine’ for CVD.
GENE RELATED TO STROKE IN STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Ikeda Katsumi , Yamori Yukio
Published: March 2003

1. In order to study genes related to stroke in stroke‐prone spontaneously hypertensive rats (SHRSP), linkage analysis was performed using F2 rats (SHRSP/Izm × WKY/Izm). The brainweight that reflected cerebral stroke in F2 rats showed cosegregation with three genetic markers, D4Mit19 (P < 0.0015), D4Mgh7 (P < 0.0014) and D4Mgh8 (P < 0.004) on chromosome 4, but not blood pressure.

2. These results suggest that a chromosomal region other than the region responsible for hypertension contributes to the development of stroke in SHRSP.
NEW MEMBERS OF UNCOUPLING PROTEIN FAMILY IMPLICATED IN ENERGY METABOLISM
Authors: Hosoda Kiminori , Itoh Hiroshi , Son Cheol , Doi Kentaro , Tanaka Tokuji , Fukunaga Yasutomo , Yamori Yukio , Nakao Kazuwa
Published: March 2003

1. The regulation of energy metabolism involves food intake and energy expenditure. Mitochondrial uncoupling proteins (UCP) are implicated in energy expenditure.

2. cDNA of a homologue of UCP highly expressed in rat skeletal muscle, UCP‐3, is isolated and sequenced. Rat UCP‐2 cDNA is also isolated and sequenced.

3. Rat UCP‐3 cDNA probe hybridized two bands, a major band at 2.5 kb and a minor band at 2.8 kb in rat tissues. The mRNA was expressed at the highest level in the skeletal muscle, and moderately in the interscapular brown adipose tissue (BAT). Only weak signals were detected in the epididymal white adipose tissue (WAT) and the heart. Rat UCP‐2 cDNA probe hybridized a 1.7 kb band detected widely in the whole body, especially abundant in the lung and the spleen. In contrast to the UCP‐3 gene expression, the UCP‐2 gene expression was expressed at substantial levels in the WAT and only at slight levels in the skeletal muscle and BAT.

4. The UCP‐3 gene expression is augmented two‐fold in the gastrocnemius muscle from rats fed a high‐fat diet (P < 0.05). The UCP‐3 mRNA levels remained unchanged in the interscapular BAT, and epididymal WAT. The levels of the UCP‐2 gene expression are augmented significantly in the epididymal WAT (1.6‐fold; P < 0.05), while no significant increase is observed in the gastrocnemius muscle and interscapular BAT.
HUMAN ERYTHROCYTE BUT NOT BRAIN ACETYLCHOLINESTERASE HYDROLYSES HEROIN TO MORPHINE
Authors: Salmon Asher Y , Goren Zafrir , Avissar Yaniv , Soreq Hermona
Published: March 2003

1. In human blood, heroin is rapidly hydrolysed by sequential deacylation of two ester bonds to yield first 6‐monoacetylmorphine (6‐MAM), then morphine.

2. Serum butyrylcholinesterase (BuChE) hydrolyses heroin to 6‐MAM with a catalytic efficiency of 4.5/min per μmol/L, but does not proceed to produce morphine.

3. In vitro, human erythrocyte acetylcholinesterase (AChE) hydrolyses heroin to 6‐MAM, with a catalytic efficiency of 0.5/min per μmol/L under first‐order kinetics. Moreover, erythrocyte AChE, but not BuChE is capable of further hydrolysing 6‐MAM to morphine, albeit at a considerably slower rate.

4. Both hydrolysis steps by erythrocyte AChE were totally blocked by the selective AChE inhibitor BW284c51 but were not blocked by the BuChE‐specific inhibitor, iso‐OMPA (tetraisopropylpyrophosphoramide).

5. The brain synaptic form of AChE, which differs from the erythrocyte enzyme in its C‐terminus, was incapable of hydrolysing heroin.

6. Heroin suppressed substrate hydrolysis by antibody‐immobilized erythrocyte but not by brain AChE.

7. These findings reveal a new metabolic role for erythrocyte AChE, the biological function of which is as yet unexplained, and demonstrate distinct biochemical properties for the two AChE variants, which were previously considered catalytically indistinguishable.
SEX‐ AND AGE‐RELATED CHANGES IN URINARY CONTENTS OF α1‐MICROGLOBULIN AND ULINASTATIN IN MICE
Authors: Shikimi Tadahiro , Suzuki Shusaku , Kaku Koichi , Ishino Hiroshi , Okunishi Hideki , Takaori Shuji
Published: March 2003

1. Using two murine strains, ICR/Jcl and senescence‐accelerated‐prone inbred mouse 1 (SAMP1), age‐associated changes in urine indices (e.g. urine volume, creatinine contents, contents of α1‐microglobulin (α1M) and ulinastatin (UT)) and the relation of urinary contents of α1M and UT were investigated.

2. Sex‐related differences in the indices were not observed in ICR nor in SAMP1 mice.

3. Urine indices per 24 h of ICR mice at 6 and 14 months of age were higher than those at 3 months of age, although indices of SAMP1 mice did not change with ageing. Urinary contents of α1M and UT in ICR mice at 6 and 14 months of age were higher than those in SAMP1 mice. However, contents of α1M and UT expressed as the contents per creatinine did not differ between these two strains.

4. In the relation between urinary contents of α1M and UT, a positive correlation was displayed both in ICR and SAMP1 mice, and the regression slope did not significantly differ with ageing in these two strains.

5. These results suggest that ageing per se is not a factor which affects the relation of urinary contents of α1M and UT.
RENAL HAEMODYNAMIC AND EXCRETORY RESPONSES TO BRADYKININ IN ANAESTHETIZED DOGS
Authors: Matsumura Yasuo , Tadano Kiyoshi , Yamasaki Tomoyuki
Published: March 2003

1. Effects of bradykinin (BK) on renal haemodynamics and urine formation were examined in anaesthetized dogs.

2. Renal arterial infusion of BK at doses of 5 or 50 ng/kg per min produced dose‐dependent increases in renal blood flow (RBF), without affecting systemic arterial pressure or glomerular filtration rate. There were also significant and dose‐dependent increases in urine flow (UF), urinary excretion of sodium (UNaV) and fractional excretion of sodium (FENa) and decreases in urine osmolality during BK infusion.

3. Renal haemodynamic and excretory responses to the BK infusion were completely abolished by the simultaneous administration of Hoe 140 (icatibant, 100 ng/kg per min intrarenally), a selective BK B2‐receptor antagonist.

4. In the presence of NG‐nitro‐L‐arginine (NOARG; 40 μg/kg per min intrarenally), a nitric oxide (NO) synthase inhibitor, BK‐induced renal vasodilative and natriuretic effects were markedly attenuated, although responses of UF and urine osmolality to BK remained unchanged. The water diuretic effect of BK was abolished in dogs given both NOARG and ibuprofen (12.5 mg/kg bolus injection plus 12.5 mg/kg per h of sustained infusion intravenously), a cyclooxygenase inhibitor.

5. These results clearly indicate that renal haemodynamic and excretory responses to BK were mediated exclusively by the B2‐receptor. Renal vasodilative and natriuretic responses are mainly linked to NO generation, while both NO and prostaglandin biosynthesis are involved in the BK‐induced water diuresis.
Gene Transfer And Models Of Gene Therapy For The Myocardium
Authors: Alexander M Yvonne , Webster Keith A , McDonald Patricia H , Prentice Howard M
Published: March 2003

1. Gene transfer into the myocardium can be achieved through direct injection of plasmid DNA or through the delivery of viral vectors, either directly or through the coronary vasculature. Direct DNA injection has proven extremely valuable in studies aimed at characterizing the activities of promoter elements in cardiac tissue and for examining the influence of the pathophysiological state of the myocardium on expression of transferred foreign genes.

2. Viral vectors, in particular adenoviruses and adeno‐associated virus, are capable of transfecting genetic material with high transduction efficiencies and have been applied to a range of model systems for in vivo gene transfer. Efficient gene transfer has been achieved into the coronary vessels and surrounding myocardium by intracoronary infusion of adenovirus.

3. Because the immunogenicity of viral vectors can limit transgene expression, much attention has been paid to strategies for circumventing this, including the development of new modified adenovirus and adeno‐associated virus vectors that do not elicit significant inflammatory responses. While cellular transplantation may prove valuable for the repair of myocardial tissue, confirmation of its value awaits establishment of a functional improvement in the myocardium following cell grafting.

4. Because gene transfer into the myocardium can now be achieved with high efficiency in the absence of significant inflammatory responses, the ability to regulate foreign gene expression in response to an endogenous disease phenotype will enable the development of new effective viral vectors with direct clinical applicability for specified therapeutic targets.
DIFFERENTIAL BLOCKING EFFECTS OF TETRODOTOXIN ON DOUBLE‐PEAKED VASOCONSTRICTOR RESPONSES TO PERIARTERIAL NERVE STIMULATION IN CANINE ISOLATED, PERFUSED SPLENIC ARTERY
Authors: Yang XIAO‐PING , Chiba SHIGETOSHI
Published: March 2003

1. In the present study, we investigated the effects of progressive inhibition of neuronal sodium channels by increasing concentrations of tetrodotoxin (TTX; 1–30 nmol/L) on the double‐peaked vasoconstrictor responses to electrical periarterial nerve stimulation in the canine isolated and perfused splenic artery.

2. Double‐peaked vasoconstrictions (biphasic vasoconstrictor responses) were consistently observed in following electrical stimulation with 30 s trains of pulses at 1–10 Hz. At low frequencies of stimulation (1–3 Hz), a submaximal concentration of 3 nmol/L TTX had no effect on the first phase of the contractile response, but almost completely inhibited the second‐phase response. At high frequencies (6–10 Hz), the two vasoconstrictor phases were almost equally inhibited by 50% by 3 nmol/L TTX. A three‐fold increase in the concentration of TTX used (10 nmol/L) abolished the second‐phase vasoconstriction at all stimulation frequencies tested, whereas this concentration of TTX failed to block the first‐phase response. Further increasing the concentration of TTX to 30 nmol/L completely blocked the remaining first‐phase response.

3. Treatment with 0.1 μmol/L prazosin did not modify the first‐phase response to any of the stimulation frequencies in the presence of 3 nmol/L TTX. Moreover, 0.1 μmol/L prazosin had no affect on the second‐phase response at low frequencies (1–3 Hz), while at high frequencies (6–10 Hz) it slightly, but significantly inhibited the second‐phase response. The vasoconstrictor responses that persisted after 3 nmol/L TTX and 0.1 μmol/L prazosin were completely suppressed by subsequent application of 1 μmol/L α,β‐methylene ATP at all stimulation frequencies (1–10 Hz).

4. In conclusion, progressive inhibition of sodium channels by increasing the concentration of TTX may exert a more preferential inhibition on adrenergic rather than purinergic components, suggesting that TTX‐sensitive sodium channels may have a more important role in determining the adrenergic rather than purinergic transmission of sympathetic nerves.
CHRONIC LEVOTHYROXIN TREATMENT IS ASSOCIATED WITH ION CHANNEL ABNORMALITIES IN CARDIAC AND NEURONAL CELLS
Authors: Dai DE‐ZAI , Hu HUI‐JUAN , Yang DONG‐MEI , Hao XUE‐MEI , Zhang GUANG‐QIN , Zhou PEI‐AI , Wu CAI‐HONG
Published: March 2003

1. We investigated the ion currents responsible for repolarization of guinea‐pig isolated myocytes (ICa) and rat hippocampal CA1 neurons (IA and IK) by means of the whole‐cell holding technique.

2. The rat hypertrophied heart, induced by levothyroxin, caused exaggerated cardiac arrhythmias after coronary ischaemia–reperfusion.

3. We found an enhanced ICa in guinea‐pig isolated myocytes and decreased IA and IK in rat hippocampal CA1 neurons following levothyroxin treatment. Blockade of the outward K+ current and an increment in inward Ca2+ current by chronic levothyroxin treatment contributed to the delayed repolarization and aggravated cardiac arrhythmias.

4. Animals treated with chronic levothyroxin may serve as pathological models for the investigation of the pattern of ion channel disorders with regard to impaired repolarization and aggravated cardiac arrhythmias.