bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimizing the Risks Associated with Significant QTc Prolongation in People with Schizophrenia: A Consensus Statement by The Cardiac Safety in Schizophrenia Group
Authors: Ames David , Camm John , Cook Peter , Falkai Peter , Gury Charles , Hurley Rod , Johnson Gordon , Piepho Robert , Vieweg Victor
Published: March 2003

Cardiac Safety in Schizophrenia Group

Objectes: This study was designed to help identify and clarify issues associated with cardiac safety in schizophrenia, particularly QTc interval prolongation; to raise awareness among psychiatrists of the cardiac issues involved in prescribing for schizophrenia and help psychiatrists minimise the potential cardiac risks associated with treating schizophrenia.

Methods: The currently available literature on cardiac dysfunction associated with antipsychotic treatments was reviewed by an independent panel of international psychiatric and cardiology experts. Following individual review, a joint meeting was held and a consensus statement produced.

Results: Prolongation of QTc interval is relatively common among antipsychotic drugs although there is marked variation in the extent to which the different agents exert their effect. If a patient is considered to be at high risk of significantly prolonged QTc interval (e.g. increasing age, female gender, comorbid cardiovascular disease) prescription of an antipsychotic drug with low QTc prolonging potential is recommended. Evaluation of a patient's risk factors for significant QTc prolongation is an important part of patient assessment at presentation. To significantly reduce the risk of morbidity and mortality from prolonged QTc interval a team approach involving the hospital emergency psychiatric care team, the office-based psychiatrist, the primary care physician, the cardiologist and the pharmacist is advocated.

Conclusions: Significant QTc interval prolongation caused by some antipsychotics is a risk factor that may lead to sudden death in patients with schizophrenia receiving these medications. Not all antipsychotic drugs prolong QTc interval. Careful clinical and pharmacological management of the patient with schizophrenia can significantly reduce the risks of morbidity and mortality from QTc interval prolongation.
A Century of Psychiatry in Queensland
Authors: Lawrence Joan
Published: March 2003

Objective: To briefly review the development of psychiatry in Queensland since its inception.

Conclusions: From a colourful and tumultuous start at the time of State-hood, Queensland has provided care for the mentally ill in keeping with the sociopolitical conditions of the era influenced by the prevailing thera-peutic approach of moral treatment and custodial care tempered with humanity. Chronic underfunding and a diverse and scattered geography have influenced service provision throughout the century. Innovation and adaptation to changing scientific knowledge, destigmatisation, integration of services, and concern about human rights, however, ensure that Queensland can face the new millennium with confidence and optimism.
Towards a Better Public Housing Service for People with Mental Illness: The Importance of Intersectoral Linkage
Authors: Meehan Tom , Drake Suzanne , Bergen Helen , Gillespie Penny , Sondergeld Suzanne
Published: March 2003

Objective: To discuss issues relevant to the equitable delivery of public housing services to people with mental illness. Strategies adopted by Queensland Department of Housing to address these issues and to improve services are described, and matters of particular relevance to mental health professionals are highlighted.

Conclusions: Formal interagency service agreements between the Departments of Health, Housing and Disability Services, appropriate training programs, and case conferencing strategies can enhance the delivery of appropriate housing services to people with mental illness. Promotion of active interagency collaboration by mental health professionals will facilitate these strategies.
Academic Departments of Psychiatry in Australia: A Need for Reinvention
Authors: Singh Bruce
Published: March 2003

Objective: To give an overview of academic departments of psychiatry in Australia, emphasising the contribution they have made to the development of psychiatry in this country and the current pressures on them.

Method: Review of the literature, historical perspective and personal observation.

Results: University departments of psychiatry are under considerable stress in Australia because of pressure on both the health and education budgets.

Conclusion: In the current climate, university departments need to reconsider their core goals and review their sources of funding if they are to survive and prosper.
Madness and James Joyce
Authors: Kaplan Robert
Published: March 2003

Objective: To consider the association between the author James Joyce and madness.

Conclusions: Joyce lived closer to the state of madness than he would have preferred. His mother died in a state of delirium. His daughter Lucia developed hebephrenic schizophrenia and was permanently hospitalised. His son married a manic depressive. Joyce, an acute observer of the world around him, portrayed different states of madness in his writings, most famously in the Nighttown chapter of Ulysses. Critics of his works accused him of being mad, interpreting his use of the stream-of-consciousness and other unique literary techniques as the product of a disordered mind. A psychiatrist referred to him as the schizoid origin of his daughter's insanity. Yet Joyce, who displayed an extraordinary discipline in writing his works, always had a clear idea of his intentions and believed his approach would ultimately be vindicated.
The Therapist's Dilemma: Be Sincere or Fake It?
Authors: Morstyn Ron
Published: March 2003

Objective: To examine the pressure on therapists to fake sincerity and the significance of genuine sincerity in psychotherapy.

Conclusions: There are many reasons why therapists might fake sincerity. We live in a post-modern culture of dissimulation and ‘playing the game’ that puts a premium on faking sincerity. Manualised and scripted psycho-therapies encourage fake sincerity, as do the measurement requirements of EBM, and the short-term approach of Managed Care. Kohut's ‘corrective emotional experience’ of empathy reinforces benevolent faked sincerity. Studies demonstrate the importance of the therapist appearing warm and genuine but do not differentiate appearance from reality. Therapists may fear that true sincerity will lead to crossing boundaries, harming patients, being poorly judged or medico-legal problems. Nevertheless, if therapists aren't willing to strive for genuine sincerity, despite all the attendant risks and possible complications, then they deny their patients the opportunity of working through the difficulties of achieving sincerity in any human relationship. Moments of true mutual sincerity in psychotherapy are healing not only because of the insight achieved but also because they restore the damaged hope that sincerity is possible. Therapists who fake sincerity ultimately leave their patients feeling alone and colluding in a mutually fake therapeutic relationship.
The Role of ECT in Schizophrenia
Authors: Keuneman Richard , Weerasundera Rajiv , Castle David
Published: March 2003

Objective: To review the place of electroconvulsive therapy (ECT) in the treatment of schizophrenia.

Conclusions: ECT is as effective, if not more so, than the antipsychotic drugs in certain clinical settings. It can be rapidly effective in acute episodes. When used alone, antipsychotics have comparable or superior efficacy to ECT alone in the short term. However, ECT possibly confers better long-term outcome. Combination treatment with antipsychotic medications and ECT is superior to either treatment alone, and is safe and effective, notably in medication resistant schizophrenia. Benefits of acute courses of ECT may be short-lived unless maintenance ECT is instituted, although there are limited data on the subject. Clinically, patients with acute onset, shorter episodes are more likely to respond to ECT. Catatonia, preoccupation with delusions and hallucinations, and a relative absence of premorbid schizoid and paranoid personality traits, are other clinical factors less strongly predictive of positive response. The presence of affective symptoms is often thought to be predictive of clinical response. However, there is little research evidence for this. While medications remain the mainstay of treatment in schizophrenia, ECT does have a clear and increasingly recognised role which requires further evaluation.
Literature and Psychiatry: The Case for a Close Liaison
Authors: Bokey Kathleen , Walter Garry
Published: March 2003

Objective: To explore, through consideration of a number of literary works, the relationship between literature and psychiatry and to discuss the advantages that an interest in literature can offer psychiatric practice

Conclusions: Literature has the potential to impart knowledge in a more direct and engaging way than other information sources, and shapes attitudes. Literature also has the ability to harm. The practice of psychiatry is enriched by increasing our awareness of literary works and appreciating the contribution that these works can make to all stakeholders in the mental health field.
Unusual extra‐axial central nervous system involvement of non‐Hodgkin’s lymphoma: Magnetic resonance imaging
Authors: Singh S , Cherian Rs , George B , Nair S , Srivastava A
Published: March 2003

The MR imaging findings in a patient with non‐Hodgkin’s lymphoma with unusual involvement of the sella, pituitary stalk and left parasellar region are reported here. On the basis of the MR imaging findings, the initial differential diagnosis included invasive pituitary adenoma, a granulomatous lesion and en plaque meningioma. Trans‐sphenoidal biopsy of the sellar mass showed chronic inflammatory changes and the patient was initially treated for tuberculosis. Because follow‐up imaging showed the lesion to be progressive, a biopsy was done of an enlarged right inguinal lymph node. This revealed non‐Hodgkin’s lymphoma.
A quality assurance audit: Phase III trial of maximal androgen deprivation in prostate cancer (TROG 96.01)
Authors: Steigler A , Mameghan H , Lamb D , Joseph D , Matthews J , Franklin I , Turner S , Spry N , Poulsen M , North J , Kovacev O , Denham J
Published: March 2003

In 1997 the Trans‐Tasman Radiation Oncology Group (TROG) performed a quality assurance (QA) audit of its phase III randomized clinical trial investigating the effectiveness of different durations of maximal androgen deprivation prior to and during definitive radiation therapy for locally advanced carcinoma of the prostate (TROG 96.01). The audit reviewed a total of 60 cases from 15 centres across Australia and New Zealand. In addition to verification of technical adherence to the protocol, the audit also incorporated a survey of centre planning techniques and a QA time/cost analysis. The present report builds on TROG’s first technical audit conducted in 1996 for the phase III accelerated head and neck trial (TROG 91.01) and highlights the significant progress TROG has made in the interim period. The audit provides a strong validation of the results of the 96.01 trial, as well as valuable budgeting and treatment planning information for future trials. Overall improvements were detected in data quality and quantity, and in protocol compliance, with a reduction in the rate of unacceptable protocol violations from 10 to 4%. Audit design, staff education and increased data management resources were identified as the main contributing factors to these improvements. In addition, a budget estimate of $100 per patient has been proposed for conducting similar technical audits. The next major QA project to be undertaken by TROG during the period 1998–1999 is an intercentre dosimetry study. Trial funding and staff education have been targeted as the key major issues essential to the continued success and expansion of TROG’s QA programme.
1998 Australian radiology workforce report
Authors: Jones D Neil , O’Donnell Chris , Stuckey John
Published: March 2003

The 1998 Australian Radiologist Workforce Survey findings form the basis of the present report, prepared by the Workforce Committee of the Royal Australian and New Zealand College of Radiologists (RANZCR). A more detailed report can be accessed through the RANZCR web site ( http://www.ranzcr.edu.au). This follows similar previously published reports by the Workforce Committee in the 1990s. The issues of radiologist workforce supply and demand are examined, and benchmarks again reviewed. One of the conclusions of the present report is a possible upcoming shortage of radiologists in Australia, due to several factors, including a possible increase in the attrition rate of an ageing radiologist population, increasing female participation in the workforce, and increasing medical imaging utilization rates. In comparison with other Organization for Economic Cooperation and Development (OECD) nations, Australia had a mid‐range supply of radiologists, and also medical imaging utilization, although there has been an increase in the latter. Australian radiologist annual workloads appear to be increasing.
Abnormal modelling of the humeral head in the tricho‐rhino–phalangeal syndrome: A new radiological observation
Authors: Paterson Anne , Thomas Paul S
Published: March 2003

The case of a 27‐year‐old female patient with tricho‐rhino‐phalangeal (TRP) type I syndrome is reported. The patient demonstrated the classical features of slowly growing hair, a bulbous nose and brachydactyly with swelling at the interphalangeal joints, but in addition showed some of the less common manifestations such as supernumerary teeth and prognathism. To the authors’ knowledge this is the first reported case in which modelling abnormalities of the proximal humerus mirror those seen in the femoral head. This adds weight to the argument that the skeletal abnormalities in TRP are part of a generalized bone dysplasia.
Incisional hernia and small bowel obstruction following laparoscopic surgery: Computed tomography diagnosis
Authors: Wicks Andrew , Voyvodic Frank , Scroop Rebecca
Published: March 2003

Incisional hernias are a relatively uncommon complication of laparoscopic surgery. Early CT diagnosis of small bowel obstruction due to incarceration in an incisional hernia after laparoscopic cholecystectomy enabled early surgery to be carried out, thereby preventing gut ischaemia and resection.
Mantle planning: Report of the Australasian Radiation Oncology Lymphoma Group film survey and consensus guidelines
Authors: Barton Michael B , Rose Alex , Lonergan Denise , Thornton Deborah , O’Brien Peter , Trotter Grant
Published: March 2003

The purpose of the present paper was to measure the variation in mantle planning in Australia and New Zealand. A chest X‐ray (CXR) of a patient in the supine position with a neck node marked by wire was sent to every radiation oncologist in Australia and New Zealand. They were to mark on the CXR the lung blocks that they would use to treat this patient, assuming that the patient had stage IA Hodgkin’s disease. These marks were compared with a small sample of radiologists who were asked to define the mediastinum on the same CXR. Radiation oncologists were also asked to complete a short questionnaire about other modifications to their treatment fields and their experience with this technique. One hundred and six films were sent out and 44 radiation oncologists replied. There was a maximum variation in the placement of their lung blocks of 6 cm. Half of the lung blocks were within a 2‐cm range. One respondent said they would not use a mantle field to treat this patient. Mediastinal coverage was inadequate in at least 50% of cases. There was a very large variation in mantle field planning practices within Australia and New Zealand. For this reason Australasian Radiation Oncology Lymphoma Group has produced consensus guidelines for mantle block design. These are appended to the present paper.
Computed tomographic cephalometric analysis of Chinese patients with obstructive sleep apnoea
Authors: Peh Wilfred Cg , Ip Mary Sm , Chu Ferdinand Sk , Chung Ka‐Fai
Published: March 2003

Variations of craniofacial and upper airway structures are recognized to contribute to the phenomenon of obstructive sleep apnoea (OSA). Most previous cephalometric studies were performed using erect lateral radiographs in Caucasian patients. The present project aims to determine cephalometric measurements, utilizing CT, in normal Chinese subjects and in Chinese patients with OSA. Computed tomography of 25 patients with OSA (proven using overnight polysomnography), and of 25 age‐, sex‐, height‐, bodyweight‐ and body mass index (BMI)‐matched control subjects were prospectively performed. Thirteen standard bony and soft‐tissue measurements were obtained from the CT lateral scout view of the head and neck, taken with each subject in the neutral supine position. The cross‐sectional area was calculated at two axial levels (velopharynx and hypopharynx). The measurements in the two groups, OSA and control subjects, were compared. The measurements for hyoid position (P = 0.00), nasal cavity length (P = 0.01), mandibular prognathism (P = 0.05), tongue size (P = 0.02), oropharyngeal airway space (P = 0.02), posterior tongue airway space (P = 0.04) and cross‐sectional areas at the level of the velopharynx (P = 0.00) and hypopharynx (P = 0.01) differed significantly between the two groups. In conclusion, CT cephalometric measurements show that certain anatomical variations in the head and neck are likely to contribute to the pathogenesis of OSA in Chinese patients.
Nuclear medicine imaging in early vertebral osteomyelitis: Still of clinical utility
Authors: McEwan Louise , Wong Joseph Ch
Published: March 2003

A case is presented of vertebral osteomyelitis in an elderly confused patient with poorly localizing signs. The lesion was not diagnosed on the initial MRI study of the spine due to poor targeting. The abnormality was detected on a bone scan the following day. This was confirmed with a gallium scan 3 days later, and also a repeat MRI study 11 days after the first MRI, using an optimized protocol over the region of interest established by the bone scan.
Malignant retroperitoneal paraganglioma: Case report and review of treatment options
Authors: Hruby George , Lehman Margot , Barton Michael , Peduto Tony
Published: March 2003

A case of retroperitoneal paraganglioma metastasizing to bone is presented. This is followed by a literature review of treatment options, including external beam radiotherapy, chemotherapy and 131I‐metaiodobenzylguanidine.
Attitudes and treatment outcome of breast conservation therapy for stage I & II breast cancer using peroperative iridium‐192 implant boost to the tumour bed
Authors: Deo SV Suryanarayana , Mohanti Bidhu K , Shukla Nootan K , Chawla Sheema , Raina Vinod , Julka Pramod K , Rath Gouya K
Published: March 2003

Breast conservation therapy for early breast cancer is an established but grossly under‐utilized treatment option in India for various reasons. Breast conservation therapy was offered to 200 suitable breast cancer patients between June 1993 and June 1998. Fifty‐one patients (25%) opted for breast conservation and the remaining preferred mastectomy. In patients agreeing to conservation therapy, surgery was performed first along with peroperative implantation of iridium‐192 to deliver a boost. Whole breast irradiation of 45 Gy was delivered 3–4 weeks after the boost. Cosmesis was assessed at the end of 6 months from completion of therapy. The main reason for refusal of breast conservation therapy was fear of recurrence in the remaining breast (60%). There were no locoregional failures in our study at a median follow up of 42 months; one patient experienced a systemic relapse. Cosmesis was good to excellent in 80% of patients. Breast conservation therapy using peroperative iridium‐192 implant provides excellent locoregional disease control and cosmesis. The results of our study indicate that patient preference for mastectomy is an important reason for the under‐utilization of breast conservation therapy in India.
Malrotation of the bowel resulting in a left‐sided caecal carcinoma presenting as a palpable intrahernial mass
Authors: Torreggiani William C , Thornton Frank , Lyburn Iain , Brenner Clare , Lee Michael J
Published: March 2003

An 86‐year‐old woman presented with a large left‐sided intrahernial mass, which was shown on CT to represent an abnormally located caecal tumour. An underlying bowel malrotation was also found explaining the left‐sided nature of the mass.
Treatment of renovascular disease with percutaneous stent insertion: Long‐term outcomes
Authors: Perkovic Vlado , Thomson Ken R , Mitchell Peter J , Gibson Robert N , Atkinson Noel , Field Peter L , Becker Gavin J
Published: March 2003

Renal artery stenosis is a common, progressive cause of hypertension and renal impairment, and is frequently treated with percutaneous transluminal dilatation and stenting. The outcome of this procedure is still being evaluated. The records of 198 consecutive patients who had stents inserted at the Royal Melbourne Hospital were analysed retrospectively, and adequate follow‐up information on 148 (75%), in whom a total of 182 renal arteries had been treated was obtained. Technical success was achieved in 144 patients (97%). Complications occurred in 19 patients (13.3%), with major complications occurring in 10 (7.0%) and one death occurring in relation to the procedure. A fall in average systolic blood pressure of 13.2 mmHg (12.1–14.3 mmHg) was seen and a fall in diastolic blood pressure of 10.1 mmHg (9.3–10.9 mmHg), without an increase in the number of antihypertensive drugs used. Renal function remained stable in the majority of patients, particularly those who had minimal baseline renal impairment. Restenosis was common after 6 months, occurring eventually in 29% of screened patients, but was not shown to affect clinical outcomes. Insertion of renal artery stents is a safe and effective treatment for renal artery stenosis.
Comparison of chronic exposures received by radiation workers using different biological end‐points with the doses recorded by TLD
Authors: Venkatachalam Perumal , Paul Solomon FD , Prabhu Balasubramonian Karthikeya , Mohankumar Mary N , Jeevanram Rani K
Published: March 2003

The frequency of different biological end‐points such as translocation, dicentrics (DC) and micronuclei (MN) was studied in 14 radiation workers and 21 non‐radiation workers. The average frequencies for different types of aberrations were significantly higher in radiation workers compared to those of respective aberrations in non‐radiation workers. Out of 14 radiation workers, eight subjects showed a dose above the detection limit as per translocation and seven subjects as per DC frequency and no patient showed a dose above the detection limit as per MN frequency. Regression analysis carried out between the recorded doses according to Thermo Luminescence Dosimeter (TLD) and the dose estimated as per translocation frequency gave a correlation coefficient of 0.32, whereas that obtained with TLD dose and the dose estimated as per DC was 0.81. When the correlation was made between the TLD dose, which was above 0.15 Gy (the detection limit for translocation), and the dose estimated as per translocation frequency in these subjects, a correlation coefficient of 0.98 was found. A similar analysis between the TLD dose above 0.5 Gy (the detection limit for DC) and the dose estimated as per DC frequency in these subjects, a correlation coefficient of 0.26 resulted. This paper discusses the reasons for the poor correlation obtained between TLD dose and dose estimated as per DC and MN frequency.
Giant bleeding renal angiomyolipoma: Diagnosis and management
Authors: Ashebu Samuel D , Dahniya Mohammed H , Elshebiny Yahaya H , Varro Joseph , Al‐khawari Hana
Published: March 2003

A case of a giant bleeding renal angiomyolipoma is presented. The patient was a 40‐year‐old Egyptian male with no clinical or radiological evidence of tuberous sclerosis. The radiological features and management, including the role of angiography are briefly discussed and the medical reviews on this subject are briefly considered.
Isolated hypoglossal nerve palsy due to skull base metastasis from breast cancer
Authors: Pavithran Keechilat , Doval Dinesh Chandra , Hukku Shelley , Jena Amarnath
Published: March 2003

We describe a 44‐year‐old woman who presented with an isolated unilateral hypoglossal nerve paralysis caused by a skull base metastasis from breast cancer. The patient had a modified radical mastectomy followed by local radiotherapy and adjuvant chemotherapy. Fourteen months later she presented with difficulty in speaking. Physical examination revealed an isolated left hypoglossal nerve paralysis. The MRI scan showed a mass lesion involving the left occipital condyle extending into hypoglossal canal.
Cardiac hydatid disease: Report of two cases
Authors: Snodgrass Duncan , Blome Steven
Published: March 2003

Cardiac involvement in hydatid disease is rare, occurring in less than 2% of cases of hydatid infection. It can occur as part of a widespread systemic infection or as an isolated event. It may be asymptomatic for a long period before presenting with a myriad of non‐specific symptoms. Imaging plays an important role in the diagnosis, surgical planning and follow up of cases. Current treatment involves attempted surgical resection (cystopericystectomy) with long‐term follow‐up chemotherapy (Albendazole). Both the disease and its surgical treatment carry a high complication rate, including rupture leading to anaphylaxis and death.
Spontaneous duodeno‐ureteric fistula
Authors: Srivastava Deep Narayan , Singh Darshendra Kumar , Wishard Navin Jonathan
Published: March 2003

Duodeno‐ureteric fistula is uncommon and its spontaneous development is extremely rare. We describe here a case of duodeno‐ureteric fistula that was successfully treated by surgery. The possible causes of its formation are discussed.
BARRIER MECHANISMS IN THE BRAIN, II. IMMATURE BRAIN
Authors: Saunders NR , Habgood MD , Dziegielewska KM
Published: March 2003

1. It is widely believed that ‘the’ blood–brain barrier is immature in foetuses and newborns.

2. Much evidence in support of this belief is based on experiments that were unphysiological and likely to have disrupted fragile blood vessels of the developing brain. Some confusion about barrier development arises from insufficient recognition that the term ‘blood–brain barrier’ describes a complex series of mechanisms controlling the internal environment of the brain.

3. We present evidence showing that the brain develops within an environment that, particularly with respect to protein, is different from that of the rest of the body and that possesses a number of unique features not present in the adult.

4. Barriers to protein at blood–brain and blood–cerebrospinal fluid (CSF) interfaces (tight junctions) are present from very early in development; immunocytochemical and permeability data show that proteins are largely excluded from extracellular space in developing brain.

5. Cerebrospinal fluid in developing brain contains high concentrations of proteins largely derived from plasma. This protein is transferred from blood by an intracellular mechanism across the epithelial cells of the immature choroid plexus. Only a small proportion of choroid plexus cells is involved. The route is an intracellular system of tubulo‐endoplasmic reticulum continuously connected across the epithelial cells only early in brain development.

6. High concentrations of proteins in CSF in developing brain are largely excluded from the brain’s extracellular space by barriers at the internal and external CSF–brain interfaces. These consist of membrane specializations between surfaces of cells forming these interfaces (neuroependyma on the inner surface; radial glial end feet on the outer surface). In contrast with tight junctions present at the blood–brain and blood–CSF barriers, at the CSF–brain barriers of the immature brain, other junctional types are involved: strap junctions in the neuroependyma and a mixture of junctions at the outer CSF–brain barrier (plate junctions, strap junctions and wafer junctions). These barriers are not present in the adult.

7. Permeability to small lipid‐insoluble molecules is greater in developing brain; more specific mechanisms, such as those involved in transfer of ions and amino acids, develop sequentially as the brain grows.
GENDER DIFFERENCES IN SYMPATHETIC NERVOUS SYSTEM REGULATION
Authors: Hinojosa‐Laborde Carmen , Chapa Irene , Lange Darrell , Haywood Joseph R
Published: March 2003

1. Females are protected against the development of hypertension. The purpose of the current review is to present the evidence for gender differences in the regulation of the sympatho‐adrenal nervous system and to determine if these differences support the hypothesis that, in females, the regulation of the sympathetic nervous system (SNS) is altered such that sympatho‐adrenal activation is attenuated or sympatho‐adrenal inhibition is augmented.

2. The central control of sympatho‐adrenal function is different in females and responses vary during the oestral and menstrual cycles. Pathways regulating the SNS appear to be less sensitive to excitatory stimuli and more sensitive to inhibitory stimuli in females compared with males.

3. Gender differences in arterial baroreflex sensitivity suggest that females may have a greater baroreflex sensitivity, such that alterations in blood pressure are more efficiently controlled than in males. Cardiopulmonary reflex inhibition of sympathetic nerve activity is greater in females, possibly resulting in a greater renal excretory function.

4. An attenuated sensitivity to adrenergic nerve stimulation, but not to noradrenaline (NA), suggests that gender differences in noradrenergic neurotransmission may protect females against sympathetic hyperactivity. Gender differences in the regulation of NA release via presynaptic α2‐adrenoceptors, the vasoconstrictor response to the cotransmitter neuropeptide Y and the clearance of catecholamines are consistent with this hypothesis.

5. Similarly, attenuated stress‐induced increases in plasma catecholamines in women suggest that females are less sensitive and/or less responsive to adrenal medullary activation. This is supported by findings of gender differences in adrenal medullary catecholamine content, release and degradation.

6. We conclude that there is strong evidence that supports the hypothesis that, in females, the regulation of the SNS is altered such that sympatho‐adrenal activation is attenuated or sympatho‐adrenal inhibition is augmented.
EFFECT OF PROPRANOLOL ON CENTRAL NEUROTRANSMITTER RELEASE IN WISTAR RATS ANALYSED BY BRAIN MICRODIALYSIS
Authors: Okuda Naoki , Kohara Katsuhiko , Mikami Hiroshi , Moriguchi Atsushi , Yamada Kazuo , Higaki Jitsuo , Ogihara Toshio
Published: March 2003

1. The effect of propranolol on amino acid neurotransmitter release in the rostral ventrolateral medulla (RVLM) was examined in urethane‐anaesthetized male Wistar rats.

2. Amino acids released in the RVLM in response to intravenous administration of propranolol (0.4 mg/kg per min; n = 6) or nitroglycerin (0.02 mg/kg per min; n = 5) were determined by the brain microdialysis method.

3. Amino acids in dialysates were analysed by high‐ performance liquid chromatography and were quantified by ultraviolet absorbance.

4. Administration of both intravenous propranolol and nitroglycerin significantly decreased arterial blood pressure. Heart rate was decreased only by propranolol.

5. The reduction in arterial blood pressure produced by intravenous propranolol was accompanied by a decrease in the release of the excitatory amino acid glutamate in the RVLM.

6. The reduction in arterial blood pressure following intravenous nitroglycerin was not accompanied by a release of glutamate.

7. There were no significant changes in the levels of other amino acids (glycine, taurine, GABA) following either propranolol or nitroglycerin.

8. The decrease in glutamate release in the RVLM may account, in part, for the central depressor mechanism of propranolol.
EFFECTS OF CICLETANINE ON THE PROGRESSION OF RENAL FAILURE IN 5–6 NEPHRECTOMIZED HYPERTENSIVE RATS
Authors: Nakamoto Hidetomo , Suzuki Hiromichi , Ohishi Akira , Katsumata Hiroshige , Sakaguchi Hiroshi , Saruta Takao
Published: March 2003

1. The effect of cicletanine, a novel antihypertensive agent with natriuretic activity, on blood pressure and progression of renal failure in 5–6 nephrectomized spontaneously hypertensive rats with salt loading was examined.

2. All nephrectomized rats were randomly assigned to one of four groups and their diet was changed from a normal‐ to a high‐salt (5.5% NaCl) diet for the next 10 weeks. Either 10 or 50 mg/kg per day cicletanine (low‐ and high‐dose cicletanine, respectively) or 10 mg/kg per day trichlormethiazide were administered to rats during this period once a day. During the experimental period, urine volume, urinary excretion of sodium, protein, prostaglandin (PG) E2 and 6‐keto‐PGF1α and systolic blood pressure (SBP) were measured every 2 weeks.

3. Systolic blood pressure was significantly reduced by the administration of trichlormethiazide and the higher dose of cicletanine, but not by the lower dose of cicletanine.

4. In contrast with changes to SBP, levels of serum creatin‐ ine in rats treated with both doses of cicletanine were significantly lower than in controls (0.57±0.12, 0.78±0.12 and 1.68±0.26 mg/dL for high‐ and low‐dose cicletanine and control, respectively).

5. Urinary excretion of both PGE2 and 6‐keto‐PGF1α were significantly increased in groups treated with high and low doses of cicletanine compared with control. In rats treated with trichlormethiazide, PGE2 and 6‐keto‐PGF1α levels were significantly decreased compared with control.

6. In contrast with changes in SBP, marked glomerular sclerosis with hyalinosis found in the control group was not ameliorated by trichlormethiazide treatment. These changes were not observed in rats treated with low‐ and high‐dose cicletanine, particularly those treated with the higher dose of cicletanine.

7. These data suggest that administration of cicletanine has a beneficial protective effect regarding the progression of renal failure, regardless of the level of blood pressure, through a direct and/or indirect action on the glomerulus.
INTRACELLULAR Ca2+ AND ADRENERGIC RESPONSIVENESS OF CARDIAC MYOCYTES IN STREPTOZOTOCIN‐INDUCED DIABETES
Authors: Ha Tuyen , Kotsanas George , Wendt Igor
Published: March 2003

1. The contractile function of diabetic hearts is impaired. In addition, the responsiveness of diabetic cardiac muscle to sympathetic stimulation is altered. Previous studies have revealed a depressed response to β‐adrenoceptor stimulation; however, the response to α‐adrenoceptor activation remains controversial. Because α‐ and β‐adrenoceptor agonists increase cardiac contractility, largely through increased mobilization of intracellular Ca2+, the aim of the present study was to investigate the effects of α‐ and β‐adrenoceptor stimulation on intracellular Ca2+ handling in cardiac myocytes from streptozotocin‐induced diabetic rats.

2. Intracellular Ca2+ was measured using fura‐2. Under basal conditions (27°C, 2.5 mmol/L extracellular [Ca2+], 0.3 Hz stimulation), there was no significant difference in resting or peak Ca2+ levels between control and diabetic cardiomyocytes. However, the time course of the intracellular Ca2+ transient was significantly prolonged in cells from diabetic hearts.

3. The β‐adrenoceptor agonist orciprenaline (at 10−7 and 10−6 mol/L) increased the amplitude of the Ca2+ transient in both groups; however, the extent of potentiation was less in diabetic compared with control cardiomyocytes. Orciprenaline decreased the duration of the transient to the same extent in both groups.

4. The α‐adrenoceptor agonist phenylephrine (at 10−7 and 10−6 mol/L) had no effect on the Ca2+ transient in control myocytes but caused a significant concentration‐dependent increase in its amplitude in diabetic cardiomyocytes. Phenylephrine had no effect on the time course of the transient in either group.

5. These results demonstrate differential effects of insulin‐ dependent diabetes on the responsiveness of cardiomyocytes to α‐ and β‐adrenoceptor stimulation. The heightened response to α‐adrenoceptor stimulation observed in diabetic cardiomyocytes may partly compensate for the diminished myocardial β‐adrenoceptor response.
ACTIONS OF ENDOTHELIN‐1 ON CULTURED RAT RENOMEDULLARY INTERSTITIAL CELLS ARE MODULATED BY NITRIC OXIDE
Authors: Maric Christine , Aldred G Peter , Antoine Arianne M , Eitle Eveline , Dean Rachael G , Williams David A , Harris Peter J , Alcorn Daine
Published: March 2003

1. Cultured renomedullary interstitial cells (RMIC) isolated from 4‐week‐old Sprague‐Dawley rat kidneys possess ETA receptors, as identified by reverse transcription–polymerase chain reaction (RT‐PCR).

2. Treatment with endothelin (ET)‐1 (10−6 mol/L) increases the intracellular inositol 1,4,5‐trisphosphate concentrations within 10 s and intracellular calcium concentrations after 7 s.

3. Endothelin‐1 (10−7 and 10−10 mol/L) induced increases in intracellular cAMP concentrations, but only in the presence of Nω‐nitro‐L‐arginine, a nitric oxide synthase (NOS) inhibitor. Addition of ET‐1 (10−10 mol/L) to the RMIC culture led to increases in intracellular cGMP concentrations through activation of NOS.

4. In the presence of ET‐1 (10−7 and 10−10 mol/L) and during NOS inhibition, RMIC responded with increased cell proliferation and extracellular matrix (ECM) synthesis. These responses were abolished by BQ‐123 (10−6 mol/L), suggesting mediation via the ETA receptor subtype. The proliferative effect of ET‐1 was also abolished by atrial natriuretic peptide (10−6 mol/L).

5. The present study provides evidence that binding of ET‐1 to ETA receptors on RMIC activates several intracellular second messenger systems that mediate cell proliferation and ECM synthesis.

6. These results also highlight an important interaction between ET‐1 and nitric oxide in the control of RMIC function.
BOTH EXTRACELLULAR ATP AND SHEAR STRESS REGULATE THE RELEASE OF NITRIC OXIDE IN RAT CAUDAL ARTERY
Authors: Kwon Young Mi , Shinozuka Kazumasa , Kagota Satomi , Yamaguchi Yu , Nakamura Kazuki , Kunitomo Masaru
Published: March 2003

1. To elucidate the physiological role of nitric oxide (NO) in regulating vascular tone, the effects of NG‐nitro‐L‐arginine methyl ester (L‐NAME), an NO synthase inhibitor, on the vasoconstrictor response to noradrenaline (NA) in rat caudal artery was examined.

2. NG‐Nitro‐L‐arginine methyl ester significantly potentiated the NA‐induced increase in perfusion pressure in the perfused caudal artery, but did not affect the NA‐induced contraction in caudal artery ring preparations. In addition, an increase in perfusion pressure mechanically produced by a stepwise increase in flow rate was not affected by L‐NAME.

3. Noradrenaline evoked a significant increase in the release of endogenous ATP and its metabolites from the perfused artery, whereas increased perfusion pressure as a result of increased flow rate did not evoke release of endogenous ATP.

4. In the presence of exogenously applied ATP, L‐NAME significantly potentiated the increase in perfusion pressure produced by increased flow rate.

5. These results indicate that perfused vascular tone is regulated by endogenous NO and suggest that extracellular ATP may participate in the synthesis and release of NO by shear stress in endothelial cells in the rat caudal artery.
TRANSCRIPTIONAL CONTROL BY CORTICOSTEROIDS OF CHIF GENE EXPRESSION IN THE RAT DISTAL COLON
Authors: Brennan Francine E , Fuller Peter J
Published: March 2003

1. Previous studies have shown that levels of CHIF mRNA are increased in the distal colon of the rat in response to corticosteroids. We have recently reported that this response occurs within 2 h of a single dose of either dexamethasone or aldosterone and that the response is mediated via both the mineralocorticoid and glucocorticoid receptors.

2. In the present study we sought to further define the nature of the various transcripts detected by a CHIF coding region cRNA probe in northern blot analysis of corticosteroid‐ stimulated colonic RNA. The identification of an intronic sequence was used to synthesize an intron‐specific cDNA probe to characterize the transcripts.

3. The presence of an intronic sequence in the originally published sequence was confirmed using coupled reverse transcriptase–polymerase chain reactions with primers spanning and within the intronic sequence. The intronic cDNA probe hybridized to the higher molecular weight transcripts detected by the cRNA probe. These transcripts are induced in response to both corticosteroids.

4. Taken together with our observations that the increase in CHIF mRNA levels in the distal colon in response to corticosteroids is not blocked by prior cycloheximide treatment, the increase in the levels of the primary transcript and partially spliced forms argues that this is a primary transcriptional response. This is the first clear demonstration of an aldosterone‐induced gene in vivo in a mammalian system.
ANGIOTENSIN RECEPTORS: MOLECULAR BIOLOGY AND SIGNALLING
Authors: Inagami Tadashi , Kambayashi Yoshikazu , Ichiki Toshihiro , Tsuzuki Satoshi , Eguchi Satoru , Yamakawa Tadashi
Published: March 2003

1. The active peptide hormone angiotensin II (AngII) is formed from its prohormone angiotensinogen by way of inactive angiotensin I. The highly specific protease, renin, responsible for the initiation of this system was elusive and considered unstable. We isolated it in a pure and stable form from the kidney of the pig, human, rat, and land submandibular glands of the mouse. It was shown that there is only one type of renin with highly stringent substrate specificity, except certain strains of the mouse which have two gene products.

2. The well‐known diversity of action of AngII can be attributed to the presence of more than two subtypes, AT1 and AT2, as well as multiple signalling pathways for both of them.

3. The first subtype AT1 was shown to mediate most of the traditionally recognized AngII functions such as vasoconstriction, electrolyte homeostasis etc.

4. Although the identification of the signalling modes of the second subtype AT2 still remains elusive, we and others have shown evidence that its action is generally antagonistic to that of AT1. AT2 inhibits AT1 (growth factor‐stimulated cell growth), AT2 attenuates the vasoconstriction induced by AT1. Since AT2 seems to mediate nitric oxide formation in the renal cells, it may initiate a natriuretic pathway in contrast to the sodium‐retaining action of AT1‐mediated AngII action.

5. Newer mechanisms and functions of these and other receptors will be clarified by the combination of molecular, cellular and integrated physiological studies.
DEVELOPMENT OF PERIPHERAL AUTONOMIC SYNAPSES: NEUROTRANSMITTER RECEPTORS, NEUROEFFECTOR ASSOCIATIONS AND NEURAL INFLUENCES
Authors: Hill Caryl E , Phillips Jacqueline K , Sandow Shaun L
Published: March 2003

1. The functional innervation of autonomic target tissues occurs early during development, at a time when both the nerves and post‐synaptic target tissues are still differentiating.

2. Physiological responses appear soon after the arrival of the first fibres when uptake and release mechanisms within the nerves are already functional. Initial responses differ from those in the mature animal, both in the form and, frequently, in the subtypes of receptors involved.

3. Results of a number of studies suggest that the initial expression of neurotransmitter receptors during development is largely independent of neural influences. Changes recorded in neurotransmitter receptor expression during development appear to be similarly independent of neural influences.

4. While signal transduction pathways coupling adrenergic neurotransmitter receptors to effector responses appear to develop independently of the nerves, the efficient coupling of muscarinic receptors often requires the action of the neurotransmitter, acetylcholine.

5. During the period of synapse formation, the neural plexus continues to expand. While developing varicosities can release the neurotransmitter, the capacity for neurotransmitter retention appears to be restricted. Developmental changes in the neurotransmitters that produce functional responses, while well known in the sweat glands, may also be seen in more subtle forms in other target tissues.

6. Ultrastructural studies suggest that close physical associations between the membranes of the release sites of the developing nerves and the target cells may form early during development when physiological responses are still immature. These close associations could enable more specific reciprocal interactions between nerves and target cells involving known and novel growth factors, neuropeptides and cytokines important in shaping the mature synaptic characteristics.
RENAL FUNCTION IN CHRONICALLY CATHETERIZED CONSCIOUS DIABETIC RATS USING CONSTANT AND SERVO‐CONTROLLED INFUSION
Authors: Garland HO , Hamilton K , Freeman S , Burns C , Cusack M , Balment RJ
Published: March 2003

1. Infusion experiments were performed on chronically catheterized conscious rats to assess kidney function before and after the induction of diabetes mellitus with streptozotocin.

2. Two infusion regimens were used, a conventional constant‐infusion protocol and a novel computer‐driven, servo‐controlled fluid replacement technique. The latter enables body fluid status to be maintained throughout a study occasion by servo‐ controlled replacement of spontaneous urinary fluid losses.

3. The chronically catheterized conscious rat infused using a servo‐controlled system appears to be the optimum model for a study of diabetic renal function. The conscious preparation circumvents problems associated with anaesthesia and acute surgery. The servo‐controlled infusion protocol maintains the altered fluid status of the diabetic condition. Both hyperfiltration and polyuria, characteristics of human diabetes often absent in anaesthetized and/or constantly infused diabetic rats, were seen in all conscious servo‐controlled diabetic animals.

4. The new regimen enables a more accurate assessment of renal function in experimental diabetes than with previous protocols. It should prove useful in future studies, particularly those assessing the role of anti‐diabetic drugs on the kidney.
EVIDENCE FOR DIRECT NEURAL REGULATION OF THE MAMMALIAN ANTERIOR PITUITARY
Authors: Ju GONG
Published: March 2003

1. The mammalian anterior pituitary was not known to be directly regulated by nervous elements until recently. Although it is generally acknowledged that there are a small number of nerve fibres in the anterior pituitary, they are considered to be autonomic in nature and are not directly involved in the regulation of the activities of the gland cells.

2. A growing body of evidence has been accumulated in the past decade, mainly from our laboratory, indicating that the anterior pituitary can be directly regulated by nerve fibres innervating it. The present article reviews the evidence for the hypothesis that there is neural–humoral dual regulation of the mammalian anterior pituitary.

3. Human, macaque monkey, dog and rat anterior pituitaries have been used for immunocytochemical studies at light and electron microscopic levels. Studies of the changes in the nerve fibres in the anterior pituitary following adrenalectomy or ovariectomy have been conducted on rats. The effects of electrical stimulation of the nerve fibres in the anterior pituitary on adrenocorticotropic hormone (ACTH) secretion have also been studied.

4. There are substantial amounts of nerve fibres in the anterior pituitary. They are in close proximity to the gland cells, including forming synapses. The number of nerve terminals are large. Adrenalectomy or ovariectomy induces an active response of the nerve fibres and electrical stimulation of the nerve fibres changes ACTH secretion.

5. It has been concluded that the anterior pituitary can be directly regulated by the innervating nerve fibres.