bluuebunny/crossref_metadata_2025 huggingface dataset:
CONTAMINATION OF BANKED FEMORAL HEAD ALLOGRAFT: INCIDENCE, BACTERIOLOGY AND DONOR FOLLOW UP
Authors: Sommerville S. M. M. , Johnson N. , Bryce S. L. , Journeaux S. F. , Morgan D. A. F.
Published: March 2003

Background: Allograft donations are not uncommonly found to be contaminated. The issue of contaminated donations from live donors at the time of surgery, and the significance of this to the patient in terms of subsequent sepsis of the arthroplasty, were examined.

Methods: The donations of femoral heads to the Queensland Bone Bank over a 9‐year period were reviewed, and the incidence and bacteriology of contamination were detailed. Clinical outcomes were determined for donors who had positive cultures at the time of retrieval and they were compared with those of culture‐negative donors.

Results: Between March 1987 and February 1996, 232 femoral heads were donated to the Queensland Bone Bank. Four specimens were sent for culture with each femoral head (surface swab of femoral head, acetabular swab, bone biopsy and capsule). In 51 cases, one or more positive cultures were obtained (22% contamination rate). The majority of organisms cultured were Staphylococcus epidermidis. One hundred and seventy donations came from surgery performed at the Princess Alexandra Hospital, and 40 femoral heads were considered contaminated. Deep infection was recorded in one of the 40 cases with contaminated donations and three out of 130 non‐contaminated donations had subsequent septic episodes.

Conclusion: The contamination rate detailed in the present report is higher than in most series. This may be due to the fact that four bacteriological specimens are taken to assess contamination. Two of these specimens are tissue samples which yielded more positive results than did the two swabs. All other series take no more than two bacteriological specimens, which are usually bone swabs. These are shown to have a poor yield of positive cultures. Therefore there is a significant underestimation of contamination rates by other bone banks. This has implications for the recipients of bone from those banks, particularly when the allograft material is not secondarily sterilized. This is important given increasing allograft usage, and the increasing numbers of revision joint arthroplasty and impaction grafting procedures being performed. Sterilization of all bone by irradiation to 25 kGy is recommended.
Fine‐Needle Aspiration Cytology for Diagnosis and Management of Palpable Breast Mass
Authors: Kanchanabat Burapa , Kanchanapitak Praween , Thanapongsathorn Wutthichai , Manomaiphiboon Anan
Published: March 2003

Background: The present study aims to clarify the use, in a developing country, of fine‐needle aspiration cytology (FNA) instead of open biopsy as a cost‐saving, reliable initial diagnostic and management tool for patients with breast mass.

Methods: A prospective study of 60 patients (71 breast masses) was carried out. The accuracy of physical diagnosis of the mass was compared with that obtained by FNA. The cytological results were analysed with the clinical profiles and pathological results.

Results: Physical examination was unreliable for the diagnosis of breast cyst (61.1% positive predictive value, 73.6% negative predictive value), which accounted for 35% of breast masses studied. Aspiration alone determined the diagnosis and management in 39% of masses. For solid breast masses benign cytological results (class I, II) were proved to be reliable (100% positive predictive value), as were malignant cytological results (class V; 100% positive predictive value). Inadequate cytology was reported for five masses (11.9%).

Conclusions: Fine‐needle aspiration should be routinely performed in all patients with breast masses. This would facilitate prompt diagnosis and treatment in one‐third of patients with breast cyst, and the benign cytological result could facilitate definite management in the majority of patients with a low risk of malignancy. This could save cost, time and patient anxiety. For the patients with a high clinical suspicion of breast cancer, the positive cytological result could reliably confirm the diagnosis, while the equivocal result could be combined with mammography or open biopsy. Considering the ease, simplicity and low cost, FNA may be suitable for developing countries where other non‐invasive procedures are unavailable or difficult to obtain, and it could replace open biopsy, which is still commonly done.
Is there a diminishing role for surgery for merkel cell carcinoma of the skin? A review of current management
Authors: Poulsen M. , Harvey J.
Published: March 2003

Merkel cell carcinoma is a highly malignant skin tumour that must be managed in a multidisciplinary forum. Excisional biopsy of the primary is recommended and this should be followed by postoperative radiotherapy to the primary site, in‐transit areas and the draining lymph nodes. The tumour is quite radiosensitive and radiation doses of the order of 50 Gy offer high levels of local control. Resection margins of 3 cm are not required provided postoperative radiotherapy is used. In the event of inoperable disease, patient refusal of surgery or a frail patient, radiotherapy should be used as the sole treatment modality, with high likelihood of achieving local control. Patients with involved nodes have a higher risk of distant disease. Traditionally, involved nodes have been managed with resection but, currently, there are protocols exploring the use of synchronous chemoradiotherapy as definitive treatment. Although adjuvant chemotherapy has been used in this setting to reduce the risk of distant seeding, the benefits at this stage have not been confirmed conclusively. The presence of distant disease carries a grave outlook and responses to chemotherapy occur frequently, but are usually shortlived.
Beyond good practice: Issues in working with people with intellectual disability and high support needs
Authors: Tannous Caterina , Lehmann‐Monck Val , Magoffin Rebecca , Jackson Olivia , Llewellyn Gwynnyth
Published: March 2003

Many more people with an intellectual disability now live in the community as a result of de‐institutionalization. Occupational therapy is one service that assists people with intellectual disabilities to participate as fully as possible in their local communities. Despite the potential benefits of occupational therapy, there is little written about the types of interventions used and the effectiveness of their outcomes with people with intellectual disabilities. The present interview study about current occupational therapy practice with people with intellectual disabilities and high support needs was conducted with experienced Australian clinicians. Positive outcomes for clients with high support needs were achieved in two ways: (i) by what therapists do; and (ii) by the features of the therapy relationship. In addition, interventions that indirectly empowered clients and changed others’ perceptions were seen to have the most positive effect. The findings are discussed with regard to current occupational therapy literature and implications for occupational practice and education are presented.
Extradural cavernous haemangioma simulating a disc protrusion
Authors: Slavotinek JP , Fowler S , Sage MR , Brophy BP
Published: March 2003

Cavernous haemangiomas confined to the epidural space are rare and are therefore infrequently considered in the differential diagnosis of spinal epidural masses. In order to draw attention to this diagnosis, a case in which an epidural cavernous haemangioma simulates a lateral/foraminal disc protrusion is presented.
Pelvi‐calyceal cast formation following silver nitrate treatment for chyluria
Authors: Gulati MS , Sharma R , Kapoor A , Berry M
Published: March 2003

A case of chyluria is reported in which anuria followed instillation of 3% silver nitrate into the collecting system of both kidneys, with unusual radiographic features. Plain radiographic, ultrasound and computed tomographic findings are discussed. To the best of the authors’ knowledge this has not been previously described in the literature.
Small cell carcinoma of the vagina
Authors: Elsaleh Hany , Bydder Sean , Cassidy Barry , Thompson Jane
Published: March 2003

A case of localized small cell neuroendocrine carcinoma of the vagina is reported. The patient was treated with concurrent chemoradiation with significant toxicity but obtained a complete response. Thirteen months after therapy the patient developed distant metastasis and died shortly thereafter. Review of the literature found that patients treated with local therapy alone had a shorter survival and died of systemic disease. As with small cell neuroendocrine carcinomas arising from other sites, systemic relapse remains an important issue that warrants combination therapies, although in pelvic sites this may be associated with an increase in side‐effects.
Management of localized low‐grade follicular lymphomas
Authors: MacManus Michael P , Seymour John F
Published: March 2003

Long‐term follow‐up data from Stanford and other centres suggest that 40–50% of patients with clinical stages I and II follicular low‐grade lymphoma can be cured by radiotherapy (RT). Relapse generally occurs outside radiation fields and most relapsed patients ultimately die from lymphoma. No randomized data exist to support adjuvant chemotherapy but only one trial of low‐intensity chemotherapy was sufficiently powerful to address the question. Nevertheless, data from a large phase‐II study from MD Anderson suggest that combined chemotherapy and RT can produce progression‐free survival results that are far superior to historical series, with survival at 10 years to be approximately 20% superior to radiation alone. These results have encouraged the development of a joint phase III study by the Trans Tasman Radiation Oncology Group (TROG) and the Australasian Leukaemia and Lymphoma Group (ALLG) in which patients with clinical stage I/II follicular lymphoma are randomized to involved field RT with or without six cycles of cytotoxic chemotherapy. In an era of rapid development in immunological and molecular therapies the potential for improved results with new combinations of more established treatment modalities should not be forgotten. This report reviews the literature on the management of localized low‐grade lymphoma and discusses the rationale for the TROG/ALLG study, which began recruitment in early 2000.
Various diffuse infiltrative lung diseases: High resolution computed tomography appearances
Authors: Tüzün Meriç , Tüzün Dilek , Hekimŏglu Baki
Published: March 2003

High resolution CT (HRCT; 1–2 mm collimation scans reconstructed with a high spatial frequency algorithm) is an established technique for the evaluation of diffuse infiltrative lung diseases. For many of these diseases, the features shown on HRCT correlate well with the histopathological abnormalities. The purpose of this pictorial essay is to illustrate HRCT appearances in various diffuse infiltrative lung diseases.
Magnetic resonance imaging of the wrist ligaments
Authors: Connell David , Page Patrick , Wright Warwick , Hoy Greg
Published: March 2003

The advent of small arthroscopes has enabled the hand surgeon to visualize the ligaments of the wrist directly with resultant increased accuracy in diagnosing and treating pathology. Orthopaedists are now demanding a preoperative assessment and this, in turn, has necessitated that radiologists have a comprehensive understanding of wrist anatomy. High resolution MR imaging can identify the wrist ligaments reliably and provide information concerning their integrity. Interpretation is not straightforward; there is considerable anatomic variation, and there are perforations, defects and degenerative tears that can be troublesome in diagnosing injury. However, with experience and attention to anatomic detail, the radiologist can provide useful information regarding structural abnormalities. When injured, the ligaments of the wrist behave as other joint ligaments do. Findings following injury include discontinuity of normal striated bands, incomplete disruption, irregularities and alteration in normal signal. Fluid pooling around a ligament and concomitant bone injury are other clues to injury. The identification of such structural abnormalities may help to explain altered biomechanics and improve the management of patients following wrist injury.
Locally advanced cervix cancer: Chemotherapy prior to definitive surgery or radiotherapy. A single institutional experience
Authors: MacLeod Craig , O'Donnell Anne , Tattersall Martin HN , Dalrymple Chris , Firth Ian
Published: March 2003

Primary or neoadjuvant chemotherapy prior to definitive local therapy has potential advantages for locally advanced cervix cancer. It can downstage a cancer and allow definitive local therapy to be technically possible (surgery), or potentially more effective (radiotherapy). It can also eradicate subclinical systemic metastases. This report reviews a single institution’s experience of neoadjuvant chemotherapy prior to definitive local therapy for cervix cancer over a 13‐year period. One hundred and six patients were treated with this intent. The patients were analysed for their response to chemotherapy, treatment received, survival, relapse and toxicity. The chemotherapy was feasible and the majority of patients had a complete or partial response (58.5%). Eight patients did not proceed to local treatment. Forty‐six patients had definitive surgery and 52 had definitive radiotherapy. The 5‐year overall survival was 27% and the majority of patients died with disease. The first site of relapse was usually in the pelvis (46.2%). Late complications that required ongoing medical therapy (n = 6) or surgical intervention (n = 2) were recorded in eight patients (7.5%). On univariate analysis stage (P = 0.04), tumour size (P = 0.01), lymph node status (P = 0.003), response to chemotherapy (P = 0.045) and treatment (P = 0.003) were all significant predictors of survival. On multivariate analysis, tumour size (P < 0.0001) and nodal status (P = 0.02) were significant predictors of survival. Despite the impressive responses to chemotherapy of advanced cervix cancer, there is evidence from randomized trials that it does not improve or compromise survival prior to radiotherapy. As its role prior to surgery remains unclear, it should not be used in this setting outside a prospective randomized trial.
Gallium avid breast carcinoma
Authors: Chan Wai‐Ling , Wadhwa Surjit S , Carolan Martin G
Published: March 2003

Primary breast carcinomas are generally thallium (Tl‐201) avid but uncommonly accumulate gallium (GA‐67). Therefore, GA‐67 scans are not routinely performed in patients with suspected breast cancer. We report a rare case of a primary breast carcinoma with bone marrow metastases where the primary lesion was GA‐67 avid but did not accumulate Tl‐201. The case also illustrated an unusual presentation of aggressive metastatic breast adenocarcinoma with pancytopenia or bone marrow failure. The extensive bone marrow metastases of the primary breast carcinoma were evident on both the Tl‐201 and GA‐67 scans.
Can virtual simulation of breast tangential portals accurately predict lung and heart volumes?
Authors: Cooke Stacey , Rattray Greg
Published: March 2003

A treatment portal or simulator image has traditionally been used to demonstrate the lung and heart coverage of the breast tangential portal. In many cases, these images were acquired as a planning session on the linear accelerator. The patients were also CT scanned to assess the lung/heart volume and to determine the surgical site depth for the electron‐boost energy. A study using 50 consecutive patients was performed comparing the digitally reconstructed radiograph (DRR) from the virtual simulation with treatment portal images. Modification to the patient's arm position is required when performing the planning CT scans due to the aperture size of the CT scanner. Virtual simulation was used to assess the potential variation of lung and heart measurements. The average difference in lung volume between the DRR and portal image was less than 2 mm, with a range of 0−5 mm. Arm position did not have a sig­nificant impact on field deviation; however, great care was taken to minimize any changes in arm position. The modification of the arm position for CT scanning did not lead to significant variations between the DRRs and portal images. The Advantage Sim software has proven capable of producing good quality DRR images, providing a realistic representation of the lung and heart volume included in the treatment portal.
EFFECT OF EXTRACELLULAR pH ON CONTRACTILE RESPONSES OF THE GUINEA‐PIG VAS DEFERENS
Authors: Nakanishi Hironori , Matsuoka Isao , Ono Tomoyuki , Kimura Junko
Published: March 2003

1. Effects of changing the pH of the bathing solution (7.0, 7.4 and 7.8) on the contractile response of the guinea‐pig isolated vas deferens to ATP, noradrenaline (NA) and ATP in the presence of NA or electrical field stimulation (EFS) were investigated.

2. Low pH tended to augment the phasic contractile response to ATP (0.01–1 mmol/L), while high pH significantly reduced the contractile response to ATP. In contrast, low pH depressed the tonic contractile response to NA (0.1–10 μmol/L), while high pH augmented the response to NA. The contractile response to 1 mmol/L ATP was markedly potentiated in the presence of 0.1–10 μmol/L NA. The potentiated contractile response to ATP in the presence of NA was unaffected by changes in pH.

3. Electrical field stimulation produced a biphasic contractile response. Low pH enhanced the initial rapid phasic contractile response to EFS, while high pH depressed the response. In contrast, the second slow tonic contractile response to EFS was unaffected by changes in pH.

4. These findings may indicate that the phasic contractile response to EFS is mainly caused by ATP while the tonic contractile response is a synergistic response to ATP and NA concomitantly released from sympathetic nerve terminals.
ADENOSINE AND PRECONDITIONING REVISITED
Authors: Miura Tetsuji , Tsuchida Akihito
Published: March 2003

1. Myocardial tolerance against infarction is substantially increased by exposing myocytes to 3–10 min transient ischaemia. In this phenomenon, termed ‘preconditioning’, the adenosine receptor is one of the redundant triggers and the best characterized factor in the cardioprotective mechanism.

2. An increase in interstitial adenosine during preconditioning is thought to be derived primarily from hydrolysis of 5′‐AMP in the myocyte by cytosolic 5′‐nucleotidase, although a contribution of ectosolic 5′‐nucleotidase remains controversial. Adenosine production during ischaemia is substantially suppressed in the preconditioned myocardium, probably due to a decrease in ATP utilization.

3. The adenosine receptor needs to be activated not only at the time of preconditioning ischaemia, but also during ischaemic insult for the preconditioning to be cardioprotective. However, the extent of cardioprotection afforded by preconditioning is primarily determined by the interstitial adenosine level achieved during preconditioning ischaemia, not by the level during sustained ischaemia. These data suggest that a post‐receptor mechanism downstream of the adenosine receptor may be up‐regulated after preconditioning.

4. Studies in vitro suggest that the subtypes of adenosine receptor relevant to preconditioning against infarction are A1 and A3, the activation of which appears to provide additive protection. The functional interrelationship between these subtypes in vivo remains unknown.

5. An important step downstream of adenosine receptor activation is protein kinase C (PKC), which facilitates opening of ATP‐sensitive potassium (KATP) channels, probably leading to enhancement of myocardial tolerance. However, activation of other protein kinases, such as tyrosine kinase, may also be important in preconditioning, depending on the animal species and preconditioning protocols. The PKC isoform and location of KATP channels (i.e. sarcolemmal vs mitochondrial KATP) that induce anti‐infarct tolerance in myocytes remain to be identified.
CO‐OPERATION BETWEEN ENDOTHELIN AND NITRIC OXIDE IN PROMOTING ENDOTHELIAL CELL MIGRATION AND ANGIOGENESIS
Authors: Goligorsky Michael S , Budzikowski Adam S , Tsukahara Hirokazu , Noiri Eisei
Published: March 2003

1. Among the diverse functions of endothelins (ET), their role in the remodelling of blood vessels remains poorly examined. In the present review, we summarize findings obtained in our laboratory and present four independent lines of evidence to support this novel function. We also demonstrate that the motogenic and angiogenic effects of ET are mediated via the ETB receptor and that the functional endothelial nitric oxide synthase (NOS) is requisite for this action.

2. We demonstrated that ET stimulates transmigration of endothelial cells in a modified Boyden chamber and accelerates endothelial wound healing acting via ETB receptors.

3. In genetically engineered Chinese hamster ovary cells expressing either ETB receptor or endothelial NOS or both, application of ET results in accelerated cell migration only when the receptor and the enzyme are coexpressed. Application of antisense oligonucleotides producing a specific knockdown of the endothelial NOS results in the loss of ET ability to stimulate endothelial cell migration in response to ET.

4. Finally, using a novel model of in vivo angiogenesis, we were able to demonstrate that ET enhances formation of new vessels, but this effect requires functional endothelial NOS.

5. The described phenomenon of NO production, serving as a prerequisite for endothelial cell locomotion in response to activation of ETB receptor may explain a host of pathophysiological observations on inadequate angiogenesis despite enhanced generation of ET‐1.

6. Based on the contribution of endothelial cell migration to angiogenesis, these data may implicate insufficient NO production in pathological states (e.g. atherosclerosis, heart failure and hypertension) in the inappropriate response to angiogenic stimuli.
ADRENOCORTICOTROPHIC HORMONE‐INDUCED HYPERTENSION IN THE RAT: EFFECTS OF THE ENDOTHELIN ANTAGONIST BOSENTAN
Authors: Fraser Tafline B , Mangos George J , Turner Steven W , Whitworth Judith A
Published: March 2003

1. The effects of the endothelin antagonist bosentan on adrenocorticotrophic hormone (ACTH)‐induced hypertension were examined in the conscious male Sprague‐Dawley rat.

2. In order to confirm endothelin antagonism, 18 rats were randomly divided into two groups: receiving either (i) endothelin‐1 (0.125, 0.25, 0.5 and 1 nmol/kg, i.v.); or (ii) endothelin‐1 at these doses following bosentan (100 mg/kg gavage) and mean arterial pressure recorded (study A). Subsequently, 40 male rats (320±5 g) were randomly divided into four groups (n = 10): (i) Sham (0.9% saline, s.c.) + 5% acacia gum gavage; (ii) ACTH (500 μg/kg per day, s.c.) + 5% acacia gum gavage; (iii) Sham injection + bosentan (100 mg/kg per day) gavage; or (iv) ACTH + bosentan. Six control days (C1–C6) were followed by 11 treatment days (T0–T10). Systolic blood pressure, water intake, urine volume, food intake and bodyweight were measured every second day (study B).

3. Bosentan significantly attenuated the endothelin‐1‐induced blood pressure rise at 0.125 nmol/kg (P < 0.05), but not at higher doses.

4. Bosentan at a dose which attenuated endothelin‐1‐induced blood pressure increase had no effect on either blood pressure or metabolic parameters in ACTH‐treated rats.

5. These results suggest that endothelin does not play a major role in ACTH‐induced hypertension.
EXPRESSION AND REGULATION OF THE SODIUM–CALCIUM EXCHANGER IN CARDIAC MICROVASCULAR ENDOTHELIAL CELLS
Authors: Kaye David M , Kelly Ralph A
Published: March 2003

1. The sodium–calcium exchanger (NCX) plays an important role in Ca2+ homeostasis. In the heart, NCX participates in the control of contraction and relaxation and in large vessel endothelial cells some data suggest that NCX could influence nitric oxide (NO) generation. In this context, the cardiac microvasculature has received considerable attention as a mediator of myocardial performance, via the release of paracrine acting factors such as NO. Therefore, the aim of the current study was to characterize NCX expression and regulation in cardiac microvascular endothelial cells (CMEC). The NCX expression was also examined in neonatal ventricular cardiomyocytes where aspects of its function and regulation have been well characterized.

2. The presence of functional NCX in CMEC was confirmed by the presence of a consistent rise in intracellular Ca2+ concentration ([Ca2+]i) in response to removal of extracellular Na+. Furthermore, NCX mRNA expression was readily detectable in CMEC.

3. In order to examine the role of possible physiological regulators of NCX expression, the effect of intracellular Ca2+ loading, caused by 24 h exposure to 10 μmol/L ouabain, was investigated. In Ca2+‐loaded CMEC, there was a substantially greater rise in [Ca2+]i during exposure to Na+‐free buffer: 33±6 versus 124±25 nmol/L% (P < 0.05), consistent with increased protein expression. Consistent with these findings, northern blot analysis confirmed the presence of a two‐fold increase in NCX mRNA in these cells.

4. These data indicate the presence of functional NCX in CMEC and identify [Ca2+]i as a potential physiological regulator of expression.
REDUCED DIETARY FAT INTAKE INCREASES PARASYMPATHETIC ACTIVITY IN HEALTHY PREMENOPAUSAL WOMEN
Authors: Pellizzer A‐M , Straznicky Ne , Lim S , Kamen Pw , Krum H
Published: March 2003

1. Hypercholesterolaemia has been associated with decreased heart rate variability, a measure of cardiac parasympathetic activity. However, the effect of perturbation of the lipid profile on autonomic function has not been examined systematically.

2. The effects of short‐term dietary lipid modification on autonomic function are studied in 25 normotensive, non‐smoking, premenopausal women with normal bodyweight. Subjects consumed either a low (L, 25%) or high fat (H, 40%) diet for 2 weeks in an open, randomized, cross‐over manner with a 2 week washout.

3. Baroreflex sensitivity was determined by gating beat‐to‐beat heart period (RR) interval and continuous non‐invasive blood pressure recordings. Heart rate variability measures of cardiac parasympathetic nervous system activity were obtained in the time (standard deviation of RR intervals, root mean square of successive differences (rMSSD)) and frequency (high frequency power) domains. All assessments were made at the same timepoint in the menstrual cycle.

4. Both low‐density lipoprotein–cholesterol and high‐density lipoprotein–cholesterol decreased significantly (P < 0.05) with increased dietary fat intake (H, 2.7±0.1 vs L, 2.2±0.1; H, 1.3±0.1 vs L, 1.1±0.1 mmol/L, respectively) as did mean arterial pressure (H, 78.1±1.5 vs L, 74.3±1.5 mmHg). Weight was unchanged by dietary lipid intake (H, 62.6±8.5 vs L, 62.3±8.3 kg, P = NS).

5. There was a significant increase in rMSSD (H, 29.6±3.4 vs L, 38.8±6.4 msec, P < 0.05) and natural logarithm of high frequency power following low fat diet (H, 4.4±0.2 vs L, 4.8±0.3 msec2, P = 0.01). Baroreflex sensitivity also increased following the low fat diet (H, 13.91±2.2 vs L, 16.9±3.2 msec/mmHg, P = 0.23).

6. Short‐term dietary lipid modification can significantly increase cardiac parasympathetic nervous system activity in healthy premenopausal women. These changes in autonomic status appear to be independent of changes in bodyweight and may be of clinical relevance considering the prognostic implications of heart rate variability in cardiovascular disease.
Brain Atrial Natriuretic Peptide Family Abolishes Cardiovascular Haemodynamic Alterations Caused By Hypertonic Saline In Rats
Authors: Sakamoto Masatoshi , Nishimura Masato , Takahashi Hakuo
Published: March 2003

1. Regional haemodynamic alterations caused by hypertonic NaCl solution (Hi‐Salt; 10%, 10 μL) injected intracerebroventricularly (i.c.v.) were investigated by using radioactive microspheres in anaesthetized rats.

2. Intracerebroventricular injections of Hi‐Salt increased regional vascular resistance of visceral organs, including the kidney, and elevated plasma levels of vasopressin.

3. Intracerebroventricular pretreatment with TCV‐11974 (50 μg/10 μL/nat), an angiotensin AT1 receptor antagonist, attenuated the pressor response and vasopressin release to subsequently injected Hi‐Salt, but did not affect regional haemodynamic effects of i.c.v. Hi‐Salt on vascular resistance.

4. In contrast, i.c.v. pretreatment with atrial natriuretic polypeptide (ANP) or type‐C natriuretic polypeptide (CNP) almost completely abolished the haemodynamic changes and vasopressin release caused by i.c.v. Hi‐Salt.

5. The present findings indicate that a natriuretic family in the brain may be involved to a great degree in the central regulation of salt‐induced hypertension in rats, while brain angiotensin II is likely to participate only in vasopressin release.
Elevation Of Striatal Interleukin‐6 and Serum Corticosterone Contents In Mptp‐Treated Mice
Authors: Kaku Koichi , Shikimi Todahiro , Kamisaki Yoshinori , Shinozuka Kazumasa , Ishino Hiroshi , Okunishi Hideki , Takaori Shuji
Published: March 2003

1. Changes in the content of striatal interleukins (IL‐1β and IL‐6) and serum corticosterone in relation to deterioration of the dopaminergic system induced by 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP; a dopaminergic neurotoxin; 20 mg/kg i.p., four administrations/12 h) in C57BL/6J mice were investigated.

2. Striatal dopamine, IL‐1β, IL‐6 and serum corticosterone were measured on days 1 and 7 post‐MPTP.

3. Dopamine depletion was more severe on day 7 than on day 1 post‐treatment.

4. Increases in IL‐6 were observed on days 1 and 7 post‐MPTP. The increase in striatal IL‐6 content varied with the extent of dopamine depletion, although the IL‐1β concentration remained unchanged compared with control values on days 1 and 7 post‐treatment.

5. Serum corticosterone was not different from control on day 1 post‐MPTP. However, marked increases in the serum corticosterone were observed on day 7 post‐treatment.

6. These results suggest that changes in striatal IL‐6 and serum corticosterone are closely associated with the severity of MPTP‐induced dopaminergic degeneration.
EFFECTS OF CHELATION WITH EDTA AND VITAMIN B THERAPY ON NITRIC OXIDE‐RELATED ENDOTHELIAL VASODILATOR FUNCTION
Authors: Green Daniel J , O’Driscoll J Gerard , Maiorana Andrew , Scrimgeour Neil B , Weerasooriya Rukshen , Taylor Roger R
Published: March 2003

1. ‘Chelation therapy’ with EDTA is being frequently used in patients with cardiovascular disease, despite limited objective evidence of effectiveness. Depressed nitric oxide (•NO)‐related endothelial function accompanies atherosclerosis, and even the vascular risk factors alone, and is improved by numerous interventions that also improve prognosis in vascular disease.

2. The aim of the present study was to determine the influence of chelation therapy with EDTA alone and EDTA in combination with B vitamins on endothelial function.

3. After a control series of saline infusions, we examined the effects of a series of EDTA infusions (1.5 g, 10 times over 6 weeks) in eight subjects with coronary artery disease. In addition, because EDTA is commonly supplemented by other components, particularly B group vitamins, we subsequently examined the effect of a similar series of vitamin‐supplemented EDTA infusions.

4. Forearm blood flow (FBF) was assessed by plethysmography and graded intrabrachial infusions of the endothelium‐dependent vasodilator acetylcholine (ACh) and the endothelium‐ independent dilator sodium nitroprusside (SNP).

5. There was no difference in vasodilation to either drug after EDTA alone compared with the control periods, but the response to ACh was augmented after combined therapy (P < 0.03,
ANOVA). The latter was accompanied by a small but consistent mean (±SEM) fall in plasma homocysteine of 1.6±0.5 μmol/L (P < 0.05).

6. The selective increase in the vasodilator response to ACh after therapy with EDTA and several B group vitamins indicates that NO‐related endothelial function was improved. The absence of response to EDTA alone suggests that the supplementary vitamins were necessary for this benefit, which may have been related to the accompanying decrease in plasma homocysteine. These results, along with the current interest in the possible cardioprotective effects of vitamins and the increasing administration of ‘chelation therapy’, call for more definitive studies on these aspects of ‘alternative medicine’.
ENDOTHELIN REGULATION OF ADRENAL FUNCTION
Authors: Hinojosa‐Laborde Carmen , Lange Darrell L
Published: March 2003

1. The goal of the present review is to recount the evidence that endothelin (ET) has a significant influence on the peripheral sympathetic nervous system by regulating the function of the adrenal medulla.

2. The presence of an active ET system in the adrenal medulla has been clearly demonstrated. Endothelin protein, mRNA, binding sites and ET‐converting enzyme have been identified in adrenal tissue and medullary chromaffin cells, suggesting that this peptide may contribute to the regulation of adrenal medullary function.

3. Studies investigating the function of ET in the adrenal gland have demonstrated that ET has a stimulatory effect on the adrenal medulla. Endothelin elicits an increase in catecholamine release from perfused intact adrenal glands as well as from cultured chromaffin cells. This effect has been shown to be mediated by ETA and ETB receptors.

4. The mechanism by which ET causes an increase in catecholamine release from the adrenal medulla appears to be independent of cholinergic activation of chromaffin cells. Endothelin has been shown to act directly at chromaffin cells to increase intracellular calcium, which results in catecholamine release.

5. Endothelin can indirectly affect catecholamine release by its effect on adrenal blood flow. Studies indicate that ET has both vasoconstrictor and vasodilator effects in the adrenal gland, which suggests a role for ET in the regulation of adrenal blood flow. Endothelin has also been proposed to participate in the selective contraction of the adrenomedullary veins, which enhances the discharge of catecholamines from the adrenal gland during activation.
Heart Valve Replacement Surgery: Past, Present And Future
Authors: Starr Albert , Fessler Cindy L , Grunkemeier Gary , He Guo‐Wei
Published: March 2003

1. The present review covers the historical and present role of valvular surgery in treating heart disease and speculates what the future may be in this very important field of cardiac surgery.

2. One of the important elements of tissue valve replacement is durability and how to analyse the valves mathematically, so that the projected durability could be described from the observed period to an extended period. We found that the Weibull distribution is a very good mathematical method of describing the deterioration of tissue valves.

3. We also can see a very marked difference among different pericardial valves. The Carpentier–Edwards pericardial valve has tremendous durability compared with the previous generation of pericardial valves, namely the Ionescu–Shiley.

4. The incidence of structural valve deterioration varies according to the age of the patient at the time of implant. A very important feature to analyse in making a clinical decision with regard to the type of valve to implant is the age of the patient at the time of implantation, because this determines their long‐term survival.

5. Another very important feature of valve replacement is the problem of valve thrombosis. This was the problem that we encountered in experimental animals and why it is so difficult to obtain a long‐term survivor with mechanical valve replacement in dogs. Now, in humans, the incidence of thrombosis of these artificial valves is extremely low.

6. Another important feature of valve replacement is the incidence of late thromboembolism (TE). Differences in reports using the same valve are greater than differences between different prostheses and the average is approximately 1.5–2%/year incidence of TE.

7. We can conclude from this review that there has been significant progress in diminishing operative mortality and enhanced long‐term survival following valve replacement over the past four decades. Increased durability of tissue valves has now become apparent, from the earliest application to the current time with glutaraldehyde‐preserved pericardial valves. The late complication rates are approximately the same with all valve types, except that there is a dimunition in the possibility for valve thrombosis for tissue valves versus mechanical valves. Finally, anticoagulation continues to be required for mechanical valve replacement and we still require more durable tissue valves and freedom from anticoagulation for mechanical valves.
Cholinergic Modulation Of Respiratory Brain‐Stem Neurons And Its Function In Sleep–Wake State Determination
Authors: Bellingham Mark C , Funk Greg D
Published: March 2003

1. Shifts in behavioural state are controlled by reciprocal changes in discharge of cholinergic and aminergic groups of brain‐stem/pontine neurons. During rapid eye movement (REM) sleep, cholinergic neurons are most active and aminergic neurons are least active.

2. Significant changes occur in the central control of breathing during REM sleep; respiration rate increases in frequency and variability, brain‐stem respiratory neuron discharge is generally enhanced and the outputs of some respiratory motor neuron pools are depressed.

3. Hypoglossal motor neurons (HM) control tongue movement and their depression during REM sleep has been implicated in obstructive sleep apnoea. The cellular basis of HM depression has been investigated in vitro and may be due to enhanced activation of cholinergic receptors or decreased activation of aminergic receptors.

4. In vitro preparations that show respiratory rhythmogenesis possess advantages for the investigation of the neurochemical basis of state‐dependent changes in respiration. Cholinergic changes in respiratory modulation of HM recorded in rhythmic brain‐stem slices from mice depend on the site of activation of cholinergic receptors.
Effect Of Hypoxia On Respiratory Activity In The Foetus
Authors: Walker David W , Lee Brenda , Nitsos Ilias
Published: March 2003

1. Breathing movements stop soon after the induction of hypoxia in foetal animals, a response attributed to the active inhibition of the respiratory centres. Separate studies using punctate lesions have identified lateral pontine and thalamic sites in foetal sheep from which respiratory inhibition may arise, but whether either of these loci are actually oxygen sensitive or whether they receive input from other regions responsive to hypoxia, has not been established.

2. FOS immunocytochemistry was used to identify neuronal pools activated by hypoxia in the brain of late‐gestation foetal and newborn sheep. FOS‐positive cells were found in the pons in regions corresponding to the medial parabrachial and Kolliker–Fuse nuclei and were shown to be catecholaminergic. Neurons in this pontine region were also activated by the piperizine drug almitrine, which, like hypoxia, inhibits respiratory output in the foetus but is a respiratory stimulant in the newborn and adult. Because these pontine neurons do not express FOS protein after challenge with hypoxia or almitrine in the newborn lamb, we argue that they are crucial to the hypoxic inhibition of respiratory activity in foetal life.

3. The role of the placenta in determining these foetal responses and how this may change at birth is discussed.
Effect Of Dopamine Agonists And Antagonists On The Lorazepam Withdrawal Syndrome In Rats
Authors: Nath C , Saxena Rc , Gupta Mb
Published: March 2003

1. The effects of dopaminergic agonists and antagonists were investigated on withdrawal signs in lorazepam‐dependent rats. Physical dependence was developed by giving lorazepam admixed with food in the following dose schedules: 10 × 4, 20 × 4, 40 × 4, 80 × 4 and 120 × 7 mg/kg, daily for x days.

2. The parameters observed during the periods of administration of lorazepam and after its withdrawal were spontaneous locomotor activity (SLA), reaction time to pain, foot shock aggression (FSA) and audiogenic seizures.

3. During the withdrawal period, rats were divided into groups of 10 rats each. One group did not receive any drug and served as the control withdrawal groups. Three other groups received, separately, one of the following dopamimetic drugs: (i) 200 mg/kg per day, i.m., L‐dihydroxyphenylalanine (DOPA; +50 mg/kg per day, i.m., carbidopa); (ii) 2 mg/kg per day, i.m., amphetamine; or (iii) 1 mg/kg per day, i.m., apomorphine. The remaining groups received one of the following dopamine antagonists: (i) 0.1 mg/kg per day, i.m., SCH 23390; (ii) 0.5 mg/kg per day, i.m., haloperidol; (iii) 0.5 mg/kg per day, i.m., centbutindol; and (iv) either 1 or 20 mg/kg per day, i.m., clozapine.

4. The withdrawal signs observed in the control group were hyperkinesia, hyperaggression and audiogenic seizures.

5. L‐Dihydroxyphenylalanine (+ carbidopa), amphetamine and apomorphine potentiated hyperaggression and audiogenic seizures. The dopamine D2 receptor antagonists haloperidol, centbutindol and clozapine (at 20 mg/kg, i.m.) blocked all withdrawal signs. The D1 receptor antagonist SCH 23390 inhibited hyperkinesia and hyperaggression. The D4 receptor antagonist clozapine (at 1 mg/kg, i.m.) had no effect on any of the withdrawal signs.

6. It may be concluded that dopamine D2 receptors exert a dominant facilitatory influence, with partial contribution of D1 receptors, on the benzodiazepine withdrawal syndrome.
Regulation Of Sodium, Calcium And Vitamin D Metabolism In Dahl Rats On A High‐Salt/Low‐Potassium Diet: Genetic And Neural Influences
Authors: Wu Xiaoyan , Vieth Reinhold , Milojevic Susan , Sonnenberg Harald , Melo Luis G
Published: March 2003

1. A dietary combination of high salt and low potassium (HSLK) exacerbates hypertension in Dahl salt‐sensitive (DS) rats and renders previously normotensive Dahl salt‐resistant (DR) rats hypertensive. In both strains, the severity of hypertension correlates with urinary calcium loss. However, the magnitude of excretory calcium losses is significantly greater in DS rats and is potentiated by chemical sympathectomy in both strains.

2. We hypothesized that a defect in vitamin D metabolism may underlie the observed strain‐dependent differences in calcium balance.

3. Arterial blood pressure (ABP), water and mineral bal‐ ance and serum concentrations of 1,25‐dihydroxyvitamin D3 (1,25(OH)2 D3) and 25‐hydroxyvitamin D3 (25(OH)D3) were measured in intact and chemically sympathectomized (6‐hydroxydopamine; 6‐OHDA) DS and DR rats after 8 weeks on a HSLK diet.

4. Chronic ingestion of this diet resulted in marked and moderate levels of hypertension in DS and DR rats, respectively. The hypertension was abated and eliminated by 6‐OHDA in the DS and DR strains, respectively. Independent of treatment, DS rats had significantly higher urinary excretion of calcium and reduced intestinal absorption of the ion compared with DR rats. The DS rats had significantly higher serum levels of 1,25(OH)2 D3 and markedly lower serum levels of 25(OH)D3 than DR rats. Chemical sympathectomy tended to increase 1,25(OH)2 D3 and to decrease 25(OH)D3 levels in both strains.

5. These data indicate a genetic difference in vitamin D metabolism between DS and DR rats. The abnormally elevated levels of 1,25(OH)2 D3 in DS rats may be an appropriate compensatory response to excessive excretory calcium loss and reduced target organ sensitivity to the hormone and may, maladaptively, directly contribute to hypertension, by stimulating vascular smooth muscle contractility.
Antihyperglycaemic And Anti‐Oxidant Properties Of Andrographis Paniculata In Normal And Diabetic Rats
Authors: Zhang Xiang‐Fan , Tan Benny Kwong‐Huat
Published: March 2003

1. Oxidative stress is believed to be a pathogenetic factor in the development of diabetic complications. In the present study, we investigated the ethanolic extract of the aerial parts of Andrographis paniculata for antihyperglycaemic and anti‐ oxidant effects in normal and streptozotocin‐induced type I diabetic rats.

2. Normal and diabetic rats were randomly divided into groups and treated orally by gavage with vehicle (distilled water), metformin (500 mg/kg bodyweight) or the extract (400 mg/kg bodyweight), twice a day for 14 days.

3. At the end of the 14 day period, the extract, like metformin, significantly increased bodyweight (P < 0.01) and reduced fasting serum glucose in diabetic rats (P < 0.001) when compared with vehicle, but had no effect on bodyweight and serum glucose in normal rats. Levels of liver and kidney thiobarbituric acid‐ reactive substances (TBARS) were significantly increased (P < 0.0001, P < 0.01, respectively), while liver glutathione (GSH) concentrations were significantly decreased (P < 0.005) in vehicle‐treated diabetic rats. Liver and kidney TBARS levels were significantly lower (P < 0.0001, P < 0.005, respectively), whereas liver GSH concentrations were significantly higher (P < 0.05) in extract‐ and metformin‐treated diabetic rats compared with vehicle‐treated diabetic rats. Andrographis paniculata significantly decreased kidney TBARS level (P < 0.005) in normal rats. Hepatic superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH‐Px) activities were significantly lower in vehicle‐treated diabetic rats compared with vehicle‐treated normal rats. The extract, as well as metformin, significantly increased the activity of SOD and CAT, but had no significant effect on GSH‐Px activity in diabetic rats. The extract and metformin did not produce significant changes in the activity of these anti‐oxidant enzymes in normal rats.

4. Our results show that oxidative stress is evident in streptozotocin‐diabetic rats and indicate that the ethanolic extract of A. paniculata not only possesses an antihyperglycaemic property, but may also reduce oxidative stress in diabetic rats.
Eicosapentaenoic Acid Stimulates Nitric Oxide Production And Decreases Cardiac Noradrenaline In Diabetic Rats
Authors: Nishimura Masato , Nanbu Akira , Komori Toshiaki , Ohtsuka Ken , Takahashi Hakuo , Yoshimura Manabu
Published: March 2003

1. The aim of the present study was to investigate whether long‐term oral administration of eicosapentaenoic acid increases nitric oxide (NO) production and affects cardiac sympathetic activity in rats with diabetes mellitus.

2. We measured changes in urinary excretion of NO3–, a stable NO metabolite, and cardiac noradrenaline (NA) concentrations in non‐diabetic rats and streptozotocin‐induced diabetic rats treated with either ethyl icosapentate (EPA‐E; 100 mg/kg per day; n = 10), a purified ethyl esterification product of eicosapentaenoic acid, or vehicle (distilled water; n = 10) for 6 weeks. The effects of NG‐nitro‐
L‐arginine (
L‐NNA), a NO synthase inhibitor, on urinary NO3– excretion and cardiac NA concentrations were also investigated in diabetic rats treated with EPA‐E.

3. Urinary NO3– excretion was higher at weeks 5 and 6 in diabetic rats treated with EPA‐E than in diabetic rats treated with vehicle (week 5: 120±8 vs 51±11 μmol/g per day, respectively (P < 0.01); week 6: 279±83 vs 73±9 μmol/g per day, respectively (P < 0.01)). Cardiac NA concentrations were higher in diabetic rats than in non‐diabetic rats and were decreased in the left atrium and both ventricles in diabetic rats treated with EPA‐E compared with control. Systemic administration of
L‐NNA abolished the increase in urinary excretion of NO3– and the decrease in cardiac NA concentrations in diabetic rats treated with EPA‐E.

4. Long‐term oral administration of EPA‐E may stimulate NO production and increased NO is likely to play a role in inhibiting enhanced cardiac sympathetic activity in diabetic rats.