bluuebunny/crossref_metadata_2025 huggingface dataset:
Opsite Flexifix: An effective adjunct in the management of pain and hypersensitivity in the hand
Authors: Boscheinen‐Morrin Judith , Shannon Jacki
Published: March 2003

Hand trauma commonly results in pain, swelling and stiffness. These sequelae of injury usually resolve uneventfully. In a small number of patients, however, pain will persist long after the initial trauma. Persisting pain has a significant impact on the patient’s ability to participate in the hand therapy programme; this, in turn, hinders restoration of hand function. Pain management strategies are numerous and draw from a wide variety of disciplines, including hand therapy (occupational therapy and physiotherapy), psychology, pharmacology and, occasionally, surgery. Opsite film has been used for a number of years in the management of pain associated with diabetic neuropathy. The types of symptoms experienced by patients with neuropathy are very similar to those described by some patients with hand injuries. For the past 12 months the authors have trialled Opsite Flexifix (Smith and Nephew) on 42 patients with varying diagnoses. Patient response to this pain‐relieving strategy has been very positive and the authors believe that inclusion of Opsite Flexifix in a pain management programme is indicated.
Carcinoma of the male breast: A review of adjuvant therapy
Authors: Vinod Shalini K , Pendlebury Susan C
Published: March 2003

The purpose of the present paper was to evaluate the characteristics and outcomes of male breast cancer patients seen for adjuvant therapy at a single institution. A retrospective review of computerized records in the Departments of Medical and Radiation Oncology at the Royal Prince Alfred Hospital (RPAH) was undertaken. Between 1983 and 1996, 24 men were referred for treatment of breast cancer. Of these, 19 had localized breast cancer, four had metastatic disease and one had ductal carcinoma in situ (DCIS). The median age was 57.5 years (range: 26–78) and median follow‐ up was 6.2 years (range: 0.6–36). Pathological staging was performed. Survival was assessed using actuarial life table analysis. Of the 19 patients who presented with localized disease, there were 12 T1 , five T2 and two T4 cancers. Eleven patients had axillary lymph node involvement. Ten patients were oestrogen receptor (ER) positive, two patients were ER negative and seven patients had unknown receptor status. All patients underwent surgery. Eleven patients received radiotherapy. The median dose and dose per fraction were 50 Gy and 2 Gy, respectively. Adjuvant systemic therapy was delivered to 10 patients, of whom nine were node‐positive. Four patients received chemotherapy alone, three patients received chemotherapy and tamoxifen, and three patients received tamoxifen only. Seven patients relapsed (one local, five distant, one both). Of the two patients with local relapses, one had received radiotherapy. Of the distant failures, four of six patients had no systemic therapy. There were only two node‐positive patients who were not given systemic treatment and both relapsed. Median survival in all patients with invasive cancer was 7.5 years, and in those with localized disease it was 7.6 years. The median survival of node‐positive patients was 3.8 years. In node‐negative patients the median survival had not been reached at a median follow‐up of 6.2 years. The majority of patients (12/14) with known receptor status were ER+, a finding that parallels those of other studies. Local control rates were 88% (7/8) in patients who had mastectomy alone and 91% (10/11) in those patients receiving adjuvant radiotherapy. Systemic therapy was found to be beneficial in patients with node‐positive disease. Chemotherapy was administered more frequently than hormonal therapy. The median survivals were consistent with those reported in other series.
Radiological classification of meniscocapsular tears of the anterolateral portion of the lateral meniscus of the knee
Authors: George J , Saw Ky , Ramlan Aa , Packya N , Tan Ah , Paul G
Published: March 2003

In an arthroscopic–MRI correlation study of acute injuries to the knee it was found that anterolateral meniscocapsular separations of the lateral aspect of the knee were missed on MRI reporting. Eighty sports‐related injuries of the knee were seen by experienced orthopaedic surgeons at the University of Malaya Medical Centre and at the National Sports Centre, Malaysia from January 1996 to July 1997. Fifty of the patients were suspected to have meniscal tears that were either lateral or medial on clinical examination and they were sent for MRI. Many of these patients were tertiary referrals. Magnetic resonance imaging examinations in 27 of the 50 patients were reported as not showing any intrasubstance or obvious meniscocapsular tears, but arthroscopy performed on them revealed anterolateral meniscocapsular tears of the lateral meniscus of varying degrees in nine of these patients. In retrospect the tears could be seen on MRI, and a pattern to the tears was noted and classified as follows. Type 0, normal; type 1, torn inferior or superior meniscocapsular attachment; type 2, both meniscofemoral and meniscotibial ligaments torn but with minimal separation of meniscus and capsule by fluid or synovitis; and type 3, marked separation of meniscus and capsule by fluid (> 3 mm). Ten patients who did not undergo arthroscopy for various personal and financial reasons underwent MRI which showed type 1 and type 2 tears, and were treated conservatively. These patients were all asymptomatic after 4–6 weeks with regard to clinical signs, suggesting a lateral meniscal tear. Magnetic resonance imaging therefore does reveal minor degrees of meniscocapsular tears anterolaterally when one understands the normal anatomy in this region.
The inter‐sonographer reliability of carotid duplex ultrasound
Authors: Thomson Holly , Woods Anthony E , Lannos John , Sage Michael
Published: March 2003

Carotid duplex ultrasound (CDUS) is a non‐invasive technique used to assess the severity of carotid artery stenosis. It has been shown to have good correlation with digital subtraction angiography (DSA) but has been criticised for its variability. One source of this is the variation in results between studies responsible for re‐validating velocity criteria to match the established treatment thresholds of internal carotid artery (ICA) stenosis. The aim of this study was to develop velocity criteria and determine the presence of inter‐sonographer variation of CDUS when grading ICA stenosis in our department. Five sonographers measured the degree of ICA stenosis with CDUS in 33 patients who also underwent DSA. Receiver operator characteristic curve analysis was used to develop optimal velocity criteria for the 50%, 70% and 90% ICA stenosis thresholds as a group and for each individual sonographer. A peak systolic velocity ratio of ≥ 3.25 was shown to have the highest accuracy (91.5%) for predicting a 70% stenosis. A moderate value of κ (0.53 ± 0.027) was calculated if the optimum velocity criterion was employed for each sonographer. There was no significant variation between the ability of sonographers to grade ICA stenosis (P > 0.05) and an excellent ICC of 0.911 was calculated. This study provides evidence to suggest that CDUS in our department is not an operator‐dependant test for the investigation of ICA stenosis.
Leiomyoma of the oesophagus in an HIV‐infected patient
Authors: Kaminski Artur M , Cameron David C , French Martin AH
Published: March 2003

Leiomyomas of the oesophagus are uncommon, and have not been reported in patients infected with the human immunodeficiency virus (HIV). A case of an oesophageal leiomyoma in an adult infected with HIV is presented.
Intra‐arterial embolization of lumbar artery pseudoaneurysm following percutaneous nephrolithotomy
Authors: Jain R , Kumar S , Phadke RV , Baijal SS , Gujral RB
Published: March 2003

The management of a patient with haematuria following percutaneous nephrolithotomy is described. The patient underwent renal angiography to assess the cause of bleeding. A pseudoaneurysm arising from first left lumbar artery was incidentally discovered, which was then successfully embolized using an indigenously fabricated metallic coil and gel foam particles in the same sitting.
Post‐traumatic lumbar nerve root avulsion
Authors: Moschilla Girolamo , Song Swithin , Chakera Turab
Published: March 2003

Lumbar nerve root avulsion is a rarely seen clinical entity that may complicate major trauma. The majority of previously reported cases have associated pelvic or lumbar vertebral fractures. Two cases of traumatic pseudomeningoceles at the lumbar level with associated avulsions of the lumbar nerve roots are presented. Both patients were involved in high velocity motor vehicle accidents. Case 1 had associated pelvic fractures but no spinal fractures and, interestingly, case 2 had no fractures of the spine or pelvis. The value of MRI in making the diagnosis is demonstrated.
In vitro study of relationship between signal intensity and gadolinium‐DTPA concentration at high magnetic field strength
Authors: Shahbazi‐Gahrouei D , Williams M , Allen BJ
Published: March 2003

Although gadolinium‐diethylene triamine pentaacetic acid (Gd‐DTPA) has been used as a contrast material in MRI, it is known that the contrast enhancement effect is not uniform for high concentrations of Gd‐DTPA. In order to evaluate the proper pulse sequences for dynamic MRI in aqueous solutions of Gd‐DTPA, blood samples and melanoma cells, the signal intensity for several concentrations of Gd‐DTPA were measured under inversion recovery (T1‐weighted) at high magnetic field strength (7.0 Tesla). For aqueous solutions of Gd‐DTPA, signal intensity correlated linearly with the concentration of Gd‐DTPA between 0 mmol/L and 4 mmol/L. Using blood and melanoma cells, signal intensity correlated non‐linearly with the concentration of Gd‐DTPA between 0 mmol/L and 1.5 mmol/L. For concentrations of more than 4 mmol/L in aqueous solutions of Gd‐DTPA, 1 mmol/L in blood and 1.5 mmol/L in melanoma, signal intensity decreased with increased Gd‐DTPA concentration.
Carcinoma breast metastatic to the hand and the foot
Authors: Asthana Sonal , Deo Suryanarayana VS , Shukla Nootan K , Raina Vinod
Published: March 2003

Metastases to the peripheral bones of the extremities are rare. Such lesions are often diagnosed as inflammatory or infective in nature. We present a report of a case of simultaneous involvement of the peripheral bones of the extremities – the talus and the thumb of the left hand – with a brief review of pathophysiology and management.
Analysis of a clinical sign in traditional Chinese medicine using Doppler ultrasound
Authors: Chen David NJ , Clarke Jill
Published: March 2003

Using Doppler ultrasound, a study was done on the characteristics of the radial pulse at the wrist in pregnant and non‐pregnant women in order to test the hypothesis that the traditional Chinese medicine ‘smooth pulse’ of pregnancy has a physiological basis. Comparison of pulse characteristics in a small series of subjects strongly supports this hypothesis.
Current status of positron emission tomography in oncology
Authors: Scott AM
Published: March 2003

Positron emission tomography (PET) has emerged as a powerful diagnostic tool in oncology patients. There is evidence of the superior utility over conventional imaging methods of the principal PET tracer 18F‐fluoro‐2‐deoxy‐glucose in the
staging of a range of cancers and monitoring disease recurrence, as well as changing
patient management to more appropriate therapy. The methods for evaluating the evidence
for PET remain complex, particularly as the standard evidence‐based approach of randomized
controlled trials is not generally applicable to imaging technologies. PET has the
potential to dramatically improve our ability to manage patients with cancer and
is also making major contributions to the development of new therapies. (Intern
Med J 2000; 31: 27–36)
ENDOTHELINS IN HEALTH AND DISEASE: AN OVERVIEW
Authors: Goldie Roy G
Published: March 2003

1. There is an ever increasing volume of evidence implicating endothelin‐1 and its isoforms in a range of disease processes. These include asthma, pulmonary and essential systemic hypertension, cardiac failure and uterine dysfunction.

2. However, it is also important to realize that the endothelins play an obligatory role in normal cellular proliferation, repair and tissue development.

3. The present brief review focuses on some of the physiological and pathophysiological mediator roles of the endothelins and provides a sketch of the receptor systems and some of the signal transduction pathways that are now known to operate following receptor activation.

4. Importantly, it is now clear that the endothelins, their receptors and synthesis and degradation pathways offer potentially important therapeutic targets.
RENIN–ANGIOTENSIN SYSTEM STIMULATES CARDIAC AND RENAL DISORDERS IN TSUKUBA HYPERTENSIVE MICE
Authors: Kai Tatsuya , Sugimura Keiichi , Shimada Seijiro , Kurooka Atsuhiro , Ishikawa Kinji
Published: March 2003

1. The role of the renin–angiotensin system (RAS) in cardiac hypertrophy and nephropathy was examined in Tsukuba hypertensive mice (THM) carrying both human renin and angiotensinogen genes.

2. Tsukuba hypertensive mice were treated with 20 mg/kg per day lisinopril, 30 mg/kg per day hydralazine or nothing. Administration of drugs was performed for 6 months from 12 weeks of age; water intake and urine volume were measured and urine albumin excretion, heart to bodyweight ratio and the glomerulosclerosis index were examined.

3. Systolic blood pressure was significantly lowered by treatment with lisinopril and hydralazine. Urine volume, water intake and urinary albumin excretion were significantly decreased by lisinopril. When hydralazine was administered to THM, these parameters were transiently decreased, but eventually reached almost the same levels as those in the untreated group. The heart to bodyweight ratio was significantly decreased by lisinopril, but not by hydralazine. The glomerulosclerosis index was significantly lowered by lisinopril, but the index in the hydralazine group was not significantly different from that in the untreated group.

4. These results suggest that the RAS plays an important role in the progression of cardiac hypertrophy in THM. In addition, the RAS may also play an important role in the progression of nephropathy; however, this may also be partially regulated by elevated blood pressure in the short term.
EFFECTS OF HEART RATE ON ARTERIAL COMPLIANCE IN MEN
Authors: Liang Yu‐Lu , Gatzka Christoph D , Du Xiao‐Jun , Cameron James D , Kingwell Bronwyn A
Published: March 2003

1. Arterial compliance is a major determinant of left ventricular afterload. In keeping with earlier experimental data obtained in isolated arterial segments, it has recently been shown in the rat that arterial compliance decreases with an increase in heart rate (HR) induced by atrial pacing.

2. To elucidate the potential relevance of this effect in humans, we investigated nine male volunteers (age 20–30 years; mean 26 years). Systemic arterial compliance (SAC) was measured with the diastolic area method and carotid‐to‐femoral and femoral‐to‐dorsalis pedis pulse wave velocities (PWV) were measured to determine regional changes in compliance. Heart rate was first lowered with intravenous metoprolol to 56±2 b.p.m. and then increased by transoesophageal atrial pacing to 80 and 100 b.p.m.

3. Increasing HR from 56±2 to 80 b.p.m. by pacing increased mean arterial pressure (MAP) from 78±2 to 98±1 mmHg (P < 0.001) and then to 102±2 mmHg (P = NS). Systemic arterial compliance fell from 0.48±0.06 to 0.33±0.04 arbitrary compliance units (ACU; P < 0.01), carotid‐to‐femoral PWV increased from 6.1±0.3 to 6.8±0.4 m/s (P < 0.001) and femoral‐to‐dorsalis pedis PWV increased from 8.9±0.4 to 10.1±0.5 m/s (P < 0.001). Pacing at 100 b.p.m did not change MAP, but did lead to a further decrease in SAC (to 0.24±0.03 ACU; P < 0.05) and further increases in carotid‐to‐femoral (7.3±0.4 m/s; P = NS) and femoral‐to‐dorsalis pedis PWV (11.3±0.4 m/s; P < 0.001).

4. We conclude that systemic, central and peripheral compliances decrease in vivo with an increase in HR induced by atrial pacing.
BIOLOGICAL AND CLINICAL ROLES OF ADRENOMEDULLIN IN CIRCULATION CONTROL AND CARDIOVASCULAR DISEASES
Authors: Eto Tanenao , Kitamura Kazuo , Kato Johji
Published: March 2003

1. Adrenomedullin (AM) is found ubiquitously in tissues and organs, especially in cardiovascular tissues and in the kidney, lung and endocrine glands. It has multifunctional biological properties, of which, its effects on the control of circulation and body fluid volume regulation seem to be the most outstanding and characteristic.

2. Acute administration of a high dose of AM induces a vasodilator depressor response, cardiac inotropic effects, diuresis and suppression of aldosterone secretion in experimental animals.

3. Long‐term continuous administration of a very low dose of AM causes vasodilation in sheep (0.5 μg/kg per h) and hypotension in rats (0.8 μg/kg per h).

4. The plasma concentration of AM increases under pathological conditions such as congestive heart failure, myocardial infarction and hypertensive and renal diseases. Under these disease conditions, AM may be produced in vascular endothelial and smooth muscle cells and in cardiac myocytes in response to volume expansion, hypertension and activated humoral factors, such as catecholamine and the renin–angiotensin system.

5. Increased AM in the circulating blood and cardiovascular tissues may counteract pathological deviation in the system that controls circulation and body fluid volume, acting against cardiovascular damage and disease.

6. Because of these beneficial properties in the cardiovascular system, AM and its pharmaceutical ligands should prove useful in the treatment of cardiovascular diseases.
EFFECTS OF ANTI‐PARKINSONIAN DRUGS ON NEUROBEHAVIOURAL CHANGES INDUCED BY BILATERAL 6‐HYDROXYDOPAMINE LESIONS IN RATS
Authors: Hayakawa T , Sugimoto Y , Chen Z , Fujii Y , Kamei C
Published: March 2003

1. Effects of anti‐Parkinsonian drugs on neurobehavioural changes induced by bilateral lesions of dopaminergic neurons were investigated in rats.

2. Dopaminergic neurons in rats were lesioned bilaterally by injection of 6‐hydroxydopamine (6‐OHDA; 8 μg) into the medial forebrain bundle at the level of the posterolateral hypothalamus. As a result, a decrease in locomotor activity and marked catalepsy and prolongation of grasping time were observed.

3. Levodopa, talipexole, bromocriptine and theophylline dose‐dependently antagonized the decrease in locomotor activity induced by bilateral 6‐OHDA lesions. These drugs also showed antagonistic effects on the appearance of catalepsy and prolongation of grasping time induced by bilateral 6‐OHDA lesions. In contrast, trihexyphenidyl showed no antagonizing effect on the neurobehavioural changes induced by 6‐OHDA lesions at any concentration tested.

4. Combined treatment with levodopa and talipexole antagonized the neurobehavioural changes induced by bilateral 6‐OHDA lesions, whereas no marked changes were observed when either drug was administered separately. The same findings were noted with the simultaneous use of either levodopa (2 mg/kg) and theophylline (2 mg/kg) or talipexole (0.005 mg/kg) and theophylline (2 mg/kg).

5. These results indicate that this model may be useful for estimating the effects of drugs in the treatment of Parkinson's disease.
Renal Effects Of Efonidipine Hydrochloride, A New Calcium Antagonist, In Spontaneously Hypertensive Rats With Glomerular Injury
Authors: Kawabata Masahiko , Ogawa Tetsuya , Han Wen‐Hua , Takabatake Toshikazu
Published: March 2003

1. To obtain some insight into the renoprotective mechanism of the new calcium antagonist efonidipine hydrochloride, we evaluated the acute effects of efonidipine on proteinuria, glomerular haemodynamics and the tubuloglomerular feedback (TGF) mechanism in anaesthetized 24–25‐week‐old spontaneously hypertensive rats (SHR) with glomerular injury.

2. Efonidipine infusion at 10 μg/kg per h following a bolus dose of 10 μg/kg, i.v., reduced systemic blood pressure (BP) and renal vascular resistance, whereas renal plasma flow (RPF), glomerular filtration rate (GFR), filtration fraction, urine volume and urinary sodium excretion were unaltered. Urinary protein excretion was clearly diminished from 163±25 to 105±24 ng/min per g kidney weight.

3. Micropuncture experiments revealed that the maximal reduction of proximal stop–flow pressure (SFP), an index of glomerular capillary pressure (Pgc), induced by loop of Henle perfusion was significantly less with efonidipine treatment (6.7±1.0% of SFP with no loop flow) than in control (23.8± 3.1%). In the presence of efonidipine, SFP at half‐maximal reduction (SFP1/2max), which approximates Pgc at the in vivo steady state tubular flow rate, remained unchanged compared with control (36.9±0.8 vs 35.3±0.7 mmHg, respectively) and the slope of dependency on mean BP was not different between control and efonidipine.

4. These results indicate that efonidipine attenuates the TGF response in SHR by dilating the afferent arteriole, thus maintaining the level of RPF and GFR despite reduced renal perfusion pressure. Constant GFR and SFP1/2max under efonidipine suggest that single nephron GFR and Pgc remain unaltered and that a marked reduction in proteinuria is achieved without changes in single nephron GFR or Pgc of superficial nephrons.
Tachykinin Receptors Mediating Contractions Of Oestrogen‐Primed Rat Uterus: Classification Using Non‐Peptide Antagonists
Authors: Fisher L , Pennefather Jn
Published: March 2003

1. The aim of the present study was to characterize the tachykinin receptors mediating contractions of the uterus from the oestrogen‐primed rat. Apparent pKB values versus mammalian tachykinins and some subtype‐selective agonists were determined for the non‐peptide NK1, NK2 and NK3 receptor antagonists SR 140333, SR 48968 and SR 142801, respectively.

2. Apparent pKB values for SR 48968 tested at concen‐ trations of 3, 10 and 30 nmol/L versus neurokinin (NKA, [Lys
5MeLeu
9Nle
10] NKA(4–10) and [Nle
10] NKA(4–10) were 8.79, 9.44 and 9.33, respectively, indicating activation of an NK2 receptor and, in the case of NKA, the possible activation of an additional receptor subtype. SR 48968 (30 nmol/L) did not affect responses to NKB (1 μmol/L), senktide (30 nmol/L), substance P (SP; 100 nmol/L) or [Sar
9Met(O2)
11] SP (100 nmol/L), indicating its selectivity at this concentration.

3. SR 140333 (1–100 nmol/L) reduced the effects of the NK1‐preferring agonists SP and [Sar
9Met(O2)
11] SP, indicating the presence of NK1 receptors. The pKB estimate versus [Sar
9Met(O2)
11] was 9.01. SR 140333 (100 nmol/L) did not affect responses to NK2 and NK3 receptor‐preferring agonists.

4. SR 142801 (100 nmol/L to 1 μmol/L) produced small rightward shifts in the log concentration–response curves to NKB, yielding an apparent pKB value of 7.0. At 1 μmol/L, SR 142801 reduced responses to the NK2 agonists, suggesting some non‐selectivity at this concentration.

5. Taken together, these data provide strong evidence that tachykinin‐induced contractions of the uterus of the oestrogen‐primed rat are mediated by NK2 receptors, with some contribution from NK1 receptors.
MEDICAL SIGNIFICANCE OF CARDIOVASCULAR FUNCTION IN HIBERNATING MAMMALS
Authors: Wang SHI‐QIANG , Zhou ZENG‐QUAN
Published: March 2003

1. The hibernating mammals inherited a stable cardiovascular function as a result of adaptation to extreme external and internal environments during hibernation.

2. The cardiovascular function of a hibernator is characterized by three distinct features: (i) tolerance of hypothermia; (ii) resistance to dysrhythmia; and (iii) endurance of hypoxia. All these have clinical relevance in cardiovascular disorders in humans.

3. We suggest that the hibernating mammal can serve as a useful animal model for research into the cardiovascular system.
SELECTIVE EFFECTS OF LOMERIZINE, A NOVEL DIPHENYLMETHYLPIPERAZINE Ca2+ CHANNEL BLOCKER, ON CEREBRAL BLOOD FLOW IN RATS AND DOGS
Authors: Hara Hideaki , Shimazawa Masamitsu , Sasaoka Masaaki , Yamada Chikaomi , Iwakura Yasushi , Sakai Takanori , Maeda Yu , Yamaguchi Takafumi , Sukamoto Takayuki , Hashimoto Munehiro
Published: March 2003

1. In the present study we examined the effects of a new Ca2+ channel blocker (lomerizine), an antimigraine drug, on cerebral cortical blood flow (CBF) in anaesthetized rats (laser Doppler flowmetry) and on vertebral blood flow in anaesthetized beagle dogs (electromagnetic flowmeter).

2. Lomerizine (1.25–10 mg/kg, p.o.) dose‐dependently increased CBF in rats without affecting blood pressure (BP) or heart rate (HR).

3. The plasma concentration of lomerizine (free base) in anaesthetized rats at 30 and 60 min after the initial administration of 5 mg/kg, p.o., times at which there was a significant increase in CBF, was similar to that reported in healthy subjects receiving lomerizine at 10 mg (2 × 5 mg)/day, p.o., a dose that significantly reduces the frequency and mean duration of headache attacks.

4. Flunarizine (10 mg/kg, p.o.) did not increase CBF significantly. Flunarizine (20 mg/kg, p.o.) did not increase CBF, but did decrease BP 30–120 min after its administration.

5. Lomerizine (2.5 and 5 mg/kg, intraduodenally) dose‐ dependently increased vertebral blood flow in dogs without significantly changing BP or HR. With 10 mg/kg intraduodenal lomerazine, vertebral blood flow remained elevated from 20 to 240 min after administration and BP was decreased from 20 to 120 min.

6. Thus, lomerizine had a greater effect on CBF than on BP and HR and, therefore, it may be clinically effective in con‐ditions associated with circulatory disturbances in the brain, such as migraine, without producing systemic effects (e.g. hypotension) generally seen with other Ca2+ channel blockers.
Glycopyrrolate Treatment Of Drooling In An Adult Male Patient With Cerebral Palsy
Authors: Neverlien Po , Sorumshagen L , Eriksen T , Grinna T , Kvalshaugen H , Lind A‐B
Published: March 2003

1. The aim of the study was to assess the effect of glycopyrrolate on drooling in an adult male patient with cerebral palsy.

2. After a thorough medical examination and consent in writing by the responsible guardian, a baseline sum score for frequency and seriousness of drooling was established over a 2 week period in addition to data on shifts of handkerchiefs, urination, defecation and observation of behaviour. Glycopyrrolate (1 mg) tablets were then administered, starting with one tablet daily the third week and increasing the daily dose by one tablet per week until a maximum of four tablets during week six and 4 days of week seven when the daily dose was reduced to two tablets for 3 days. For the four weeks 8–11 three tablets were given daily. In week 12 the dose was reduced to two tablets and for the weeks 13–15 no tablets of glycopyrrolate were given.

3. For as long as the patient received three to four tablets of glycopyrrolate daily, drooling was markedly reduced and handkerchiefs were not necessary on some days. After the tablets were withdrawn drooling increased to approximately the same level as it was before treatment. No adverse medical, psychological, or social effects were observed.

4. For shorter periods, glycopyrrolate can be given in controlled doses provided that an adequate medical assessment has been undertaken.
Inhibition Of Kinin Degradation On The Luminal Side Of Renal Tubules Reduces High Blood Pressure In Deoxycorticosterone Acetate Salt‐Treated Rats
Authors: Nakajima Shinichi , Ito Hiroshi , Hayashi Izumi , Kuribayashi Yoshikazu , Okumura Toshiaki , Yajima Yoshitada , Katori Makoto , Majima Masataka
Published: March 2003

1. To determine whether the antihypertensive response in deoxycorticosterone acetate (DOCA) salt‐treated rats was mediated by kinins on the luminal side of renal tubules or in the circulation, selective urinary kininase inhibitors were administered to normal Brown Norway Kitasato (BN‐Ki) rats and kininogen‐deficient Brown Norway Katholiek (BN‐Ka) rats.

2. Kinins were degraded by neutral endopeptidase (NEP) and carboxypeptidase Y‐like kininase (CPY) in urine, but were inactivated mainly by angiotensin‐converting enzyme (ACE) in the plasma.

3. Ebelactone B inhibited CPY, while poststatin inhibited CPY and NEP.

4. Daily administration of poststatin (5 mg/kg per day, s.c.) for 3 days reduced blood pressure (BP) in DOCA salt‐treated BN‐Ki rats, but not in BN‐Ka rats.

5. Ebelactone B (5 mg/kg per day, s.c.) also reduced BP in BN‐Ki rats, which was accompanied by increased urinary sodium excretion, but had no effect on BP in BN‐Ka rats.

6. Lisinopril (5 mg/kg per day, s.c.) had no effect on BP in either rat strain.

7. Arterial kinin levels in BN‐Ki rats increased significantly (2.2–4.6 pg/mL) with captopril (10 mg/kg, s.c.). However, arterial kinin levels that induced hypotension following the infusion of bradykinin (1000 ng/kg per min, i.v.) were 110‐ fold higher than endogenous arterial kinin levels attained following captopril.

8. These results suggest that inhibition of kinin degradation on the luminal side of the renal tubules may effectively attenuate hypertension.
Circumventricular Organs: Definition And Role In The Regulation Of Endocrine And Autonomic Function
Authors: Ganong William F
Published: March 2003

1. The circumventricular organs (CVO) are structures that permit polypeptide hypothalamic hormones to leave the brain without disrupting the blood–brain barrier (BBB) and permit substances that do not cross the BBB to trigger changes in brain function.

2. In mammals, CVO include only the median eminence and adjacent neurohypophysis, organum vasculosum lamina terminalis, subfornical organ and the area postrema.

3. The CVO are characterized by their small size, high permeability and fenestrated capillaries. The subcommissural organ is not highly permeable and does not have fenestrated capillaries, but new evidence indicates that it may be involved in the hypertension produced by aldosterone acting on the brain.

4. Feedback control of corticotropin‐releasing hormone (CRH) secretion is exerted by free steroids diffusing into the brain, but substances such as cytokines and angiotensin II act on CVO to produce increases in CRH secretion. Gonadal steroids also diffuse into the brain to regulate gonadotrophin‐releasing hormone secretion. Thyrotropin‐releasing hormone secretion is regulated by thyroid hormones transported across cerebral capillaries. However, CVO may be involved in the negative feedback control of growth hormone and prolactin secretion.
Angiotensin Ii Modulation Of The Arterial Baroreflex: Role Of The Area Postrema
Authors: Bishop Vernon S , Sanderford Max G
Published: March 2003

1. Resetting the operating point of the arterial baroreflex appears to be an important factor involved in determining the level of sympathetic outflow.

2. Substantial data indicate that circulating angiotensin (Ang)II can reset the arterial baroreflex to higher operating pressures.

3. This action of AngII to increase the level of sympathetic nervous system outflow relative to blood pressure may contribute to elevated mean arterial pressure (MAP) during AngII hypertension, as well as to the maintenance of MAP during low sodium states.

4. In most instances, the resetting observed during elevated peripheral AngII is dependent on the area postrema (AP).

5. Although the central mechanisms by which the arterial baroreflex resets to different operating pressures remain to be completely defined, the AP may provide a separate mechanism whereby humoral factors can modulate the operating point of the arterial baroreflex.
Cardiovascular Effects Of Chronic Nitric Oxide Synthase Inhibition In Genetically Hypertensive Rats
Authors: Orange Stefan J , Ledingham Janet M , Laverty Richard
Published: March 2003

1. The possible role of an endothelial defect in the hypertension of the New Zealand genetically hypertensive (GH) rat strain was assessed by examining cardiovascular responses to the nitric oxide synthase (NOS) inhibitor Nω‐nitro‐
L‐arginine methyl ester (
L‐NAME) and the endothelium‐dependent depressor agent acetylcholine (ACh). The vascular sensitivity of the hindquarter to nitric oxide (NO) was examined using the NO donor sodium nitroprusside (SNP).

2. NG‐Nitro‐
L‐arginine methyl ester (10 mg/kg per day in drinking water) was given to GH and normotensive (N) rats from age 7–9 weeks, with GH and N untreated control groups. Systolic blood pressure (tail‐cuff) was monitored weekly from age 5–9 weeks. At age 9 weeks, pressure responses to various vasoactive agents were measured in vivo and in the rat isolated hindquarter. Left ventricular (LV) mass was measured at the time of death.

3. NG‐Nitro‐
L‐arginine methyl ester induced a greater hypertensive effect in GH (P < 0.001) compared with N (P < 0.05) rats and caused a significant increase in hindquarter perfusion pressure in GH rats only (P < 0.01).

4. Genetically hypertensive rats had LV hypertrophy that was exacerbated by L‐NAME (P < 0.01). Left ventricular hypertrophy was not induced by
L‐NAME in N rats.

5. The normalized response to ACh did not differ between GH and N control rats and was unaffected by L‐NAME treatment in vivo and in vitro except at the highest ACh dose (3 μg/kg) in GH hindquarters (P < 0.01). The response to SNP was similar in GH and N hindquarters and enhanced by
L‐NAME in GH (0.1 μg; P < 0.05) and N rats (0.01 μg, P < 0.01; 0.1 μg, P < 0.001).

6. These results suggest that the L‐arginine/NO system is not deficient in GH rats and that endothelial function in the GH hindquarter is preserved. They confirm that NO is involved in mediating blood pressure in GH and N rats and raise the possibility that a non‐NO‐mediated mechanism may underlie ACh‐induced vasodilation in GH and N.
Basilar Artery Remodelling In The Genetically Hypertensive Rat: Effects Of Nitric Oxide Synthase Inhibition And Treatment With Valsartan And Enalapril
Authors: Ledingham JM , Laverty R
Published: March 2003

1. The structure of the basilar artery and the relationship of structure to blood pressure and ventricular hypertrophy was examined in genetically hypertensive (GH) rats, their control normotensive (N) Wistar strain, GH given the nitric oxide synthase (NOS) inhibitor, NG‐nitro‐
L‐arginine methyl ester (
L‐NAME) and GH given
L‐NAME and either valsartan or enalapril.

2. Systolic blood pressure (SBP; tail‐cuff) was measured weekly from age 7–12 weeks. At the end of the experiment at 12 weeks, the basilar artery was fixed by perfusion and embedded in Technovit (Heraeus Kulzer GmbH, Werheim, Germany). Serial sections were cut and stained and stereological analysis applied to quantify the morphology of the vessels. Left ventricular (LV) mass was determined.

3. Both SBP and LV mass were significantly increased in GH compared with N (P < 0.001) and increased further in GH given
L‐NAME (P < 0.05). The GH
L‐NAME + valsartan and GH
L‐NAME + enalapril groups had significantly lower (P < 0.001) SBP and LV mass than the GH
L‐NAME group.

4. Basilar arteries in GH (which are frankly hypertensive, but have no apparent endothelial defect) showed hypotrophic inward remodelling compared with the N control group with no change in media to lumen ratio.

5. In the GH L‐NAME group, further inward remodelling occurred and the media to lumen ratio was increased compared with N (P < 0.01) and GH (P < 0.05). Valsartan treatment in GH
L‐NAME rats caused eutrophic outward remodelling. Enalapril caused hypertrophic outward remodelling, suggesting that the angiotensin II‐stimulated growth was not entirely suppressed with an angiotensin‐converting enzyme inhibitor or that there was a bradykinin effect with enalapril.

6. In GH with an endothelial defect induced by treatment with L‐NAME, the further remodelling, together with an increased media to lumen ratio and the development of a stroke‐like syndrome, indicates the NOS‐inhibited GH rat may be a useful model for essential hypertension (where it is known that endothelial abnormalities exist) and where stroke can develop as a consequence of the hypertension.
Physiological Effects Of Extracellular Nucleotides In The Inner Ear
Authors: Housley Gary D
Published: March 2003

1. Electrochemical homeostasis, sound transduction and auditory neurotransmission in the cochlea are influenced by extracellular purines and pyrimidines.

2. Evidence that ATP and related nucleotides influence inner ear function arises from a considerable number of cellular, molecular and physiological studies in vitro and in vivo.

3. With a full understanding of these processes, which include ionotropic (P2X receptor) and metabotropic (P2Y receptor) signal transduction pathways, signal termination involving ecto‐nucleotidases and recycling via nucleoside transporters, exciting possibilities emerge for treating hearing disorders, such as Menière’s disease, tinnitus and sensorineural deafness.
Mechanisms Of α,β‐Methylene ATP‐Induced Inhibition In Rat Ileal Smooth Muscle: Involvement Of Intracellular Ca2+ Stores In Purinergic Inhibition
Authors: Storr M , Franck H , Saur D , Schusdziarra V , Allescher H‐D
Published: March 2003

1. In order to investigate purinergic effects on rat ileal smooth muscle, we used α,β‐methylene ATP (α,β‐MeATP), ATP, ADP and UTP. α,β‐Methylene ATP and ATP were the only agonists that caused a concentration‐dependent inhibition of carbachol‐precontracted smooth muscle. The inhibitory effect of α,β‐MeATP was completely blocked by pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (3 × 10–5 mol/L), a selective antagonist of the P2X > > P2Y receptor.

2. Using reverse transcription–polymerase chain reaction we demonstrated the presence of both, P2X and P2Y receptor mRNA within the rat ileal longitudinal muscle/myenteric plexus layer preparation.

3. The α,β‐MeATP‐induced inhibition was blocked in a concentration‐dependent manner in the presence of the K+ channel blocker apamin, but was unaffected by other K+ channel blockers, such as charybdotoxin (10–7 mol/L), 4‐aminopyridine (10–4 mol/L), glibenclamide (10–5 mol/L) and tetraethylammonium (10–3 mol/L).

4. The α,β‐MeATP‐induced inhibition was unaffected by pretreatment with atropine (10–6 mol/L), phentolamine (10–6 mol/L), propranolol (10–6 mol/L), nitrendipine (10–7 mol/L), pertussis toxin (10–6 mol/L) NG‐nitro‐
L‐arginine (3 × 10–4 mol/L) and tetrodotoxin (10–6 mol/L), excluding an involvement of adrenergic, cholinergic, neural, nitrinergic or G‐protein involvement in purinergic‐mediated inhibition.

5. In order to investigate whether the internal Ca2+ stores participated in the inhibitory effect observed, we depleted internal Ca2+ stores with cyclopiazonic acid, a specific Ca2+‐ATPase inhibitor. The inhibitory effect of α,β‐MeATP was completely abolished after depletion of the intracellular Ca2+ stores.

6. This is in contrast with the effects seen for neurotensin, where neurotensin‐induced inhibition was unchanged after depletion of intracellular Ca2+ stores, suggesting at least two different pathways of apamin‐sensitive non‐adrenergic, non‐cholinergic inhibition in rat ileal smooth muscle.

7. According to our results, the inhibitory effect of α,β‐MeATP in rat ileum longitudinal smooth muscle is mediated via a P2 purinoceptor, most likely a P2X receptor, involves G‐protein‐independent activation of an apamin‐sensitive K+ channel and requires filled intracellular Ca2+ stores.
Cardioprotective Effects Of Nicorandil In Rabbits Anaesthetized With Halothane: Potentiation Of Ischaemic Preconditioning Via KATP Channels
Authors: Nakae Ichiro , Takaoka Atsushi , Mitsunami Kenichi , Yabe Takahiro , Ito Makoto , Takahashi Masayuki , Matsumoto Tetsuya , Omura Tomoko , Yokohama Hiroshi , Kinoshita Masahiko
Published: March 2003

1. The roles of ATP‐sensitive K+ channels (KATP channels) in ischaemic or pharmacological preconditioning in the rabbit heart remain unclear. Infarct limitation by ischaemic preconditioning was abolished by the KATP channel blocker glibenclamide under ketamine/xylazine anaesthesia, but not under anaesthesia induced by pentobarbital. Infarct limitation by the KATP channel opener pinacidil was detected under ketamine/xylazine anaesthesia, but not under pentobarbital anaesthesia. Thus, these effects appear to be anaesthetic dependent.

2. In the present study, we examined whether nicorandil (a KATP channel opener nitrate) exhibits cardioprotective actions under halothane anaesthesia, another commonly used volatile anaesthetic. Control animals were subjected to 40 min coronary occlusion and 120 min reperfusion. Before 40 min ischaemia, the nicorandil group received nicorandil (100 μg/kg per min, i.v., for 10 min), the 5′ preconditioning (PC) group received 5 min ischaemia/20 min reperfusion, the 2.5′PC group received 2.5 min preconditioning ischaemia/20 min reperfusion, the nicorandil + 2.5′PC group received both nicorandil and 2.5 min ischaemia/20 min reperfusion, the nicorandil + 2.5′PC + 5‐hydroxydecanoate (5HD) group received both nicorandil and 2.5 min ischaemia/20 min reperfusion in the presence of 5‐hydroxydecanoate (5HD; a KATP blocker) and the 5HD group received 5 mg/kg, i.v., 5HD alone. Myocardial infarct size in control (n = 7), nicorandil (n = 5), 5′PC (n = 8), 2.5′PC (n = 5), nicorandil + 2.5′PC (n = 5), nicorandil + 2.5′PC + 5HD (n = 5) and 5HD (n = 4) groups averaged 44.4±3.6, 41.7±5.7, 17.8±3.2,* 34.1±4.8, 21.3±4.2,* 39.1±5.6 and 38.9±5.0% of the area at risk, respectively (*P < 0.05 vs control).

3. Thus, nicorandil alone did not have an infarct size‐ limiting effect in halothane‐anaesthetized rabbits. However, the results suggest that even when nicorandil alone does not demonstrate a direct cardioprotective effect, it may enhance ischaemic preconditioning via KATP channels.
Electrophysiological Characteristics Of The Ca2+‐Activated Cl– Channel Family Of Anion Transport Proteins
Authors: Fuller Catherine M , Benos Dale J
Published: March 2003

1. A protein isolated from the bovine tracheal epithelium behaves as a Ca2+‐activated Cl– channel (CaCC) when incorporated into planar lipid bilayers.

2. An antibody raised against this protein was used to screen a cDNA expression library and resulted in the isolation of a cDNA clone that exhibited nearly identical electrophysiological characteristics to the isolated endogenous protein when expressed.

3. Recent cloning of several related proteins has revealed that the cloned bovine CaCC is one of a large and growing family. All new family members so far examined are associated with the appearance of a novel Ca2+‐mediated Cl– conductance when heterologously expressed.

4. This new group of proteins may underlie the Ca2+‐mediated Cl– conductance upregulated in the cystic fibrosis (CF) knockout mouse and thought to be responsible for the escape from the significant airway pathology associated with CF.
Species Differences In The Actions Of Sensory Neuropeptides On Contractility Of The Smooth Muscle Of The Rat And Guinea‐Pig Prostate
Authors: Ventura Sabatino , Lau Winnie Ak , Buljubasich Sretna , Pennefather Jocelyn N
Published: March 2003

1. The present review describes the actions of sensory neuropeptides on the contractility of the rat and guinea‐pig prostate gland and discusses the differences in sensitivity of the smooth muscle of the prostates taken from these species to these neuropeptides.

2. Nerve fibres immunoreactive for the tachykinins substance P and neurokinin A, as well as for the sensory neuropeptide calcitonin gene‐related peptide (CGRP), are sparsely distributed throughout the fibromuscular stroma of the prostate gland in both the rat and guinea‐pig.

3. In functional experiments, tachykinin agonists potentiate electrical field stimulation‐induced contractile responses of prostates taken from guinea‐pigs, but have no effect on those taken from rats. This potentiation is through stimulation of tachykinin NK1‐receptors.

4. Conversely, CGRP inhibits electrical field stimulation‐induced contractile responses of prostates taken from rats, but has no effect on those taken from guinea‐pigs.

5. It is concluded that although the sensory innervation to the prostate glands of the rat and guinea‐pig appears similar, the nature and sensitivity of the contractile response of the prostatic smooth muscle to applied sensory neuropeptides is vastly different in the two species.
The Compromised Intra‐Uterine Environment: Implications For Future Lung Health
Authors: Harding R , Cock ML , Louey S , Joyce BJ , Davey MG , Albuquerque CA , Hooper SB , Maritz GS
Published: March 2003

1. Epidemiological studies of infants, children and adults indicate that prenatal compromises that restrict fetal growth and cause low birthweight increase the risk of respiratory deficiencies after birth.

2. It is apparent that the lung has a limited ability to recover from early developmental compromises and that altered development can permanently impair lung architecture.

3. Lung development in utero can be adversely affected by factors associated with fetal growth restriction, namely fetal hypoxaemia, reduced substrate supply and hypercortisolaemia.

4. We have conducted a series of studies of respiratory development in chronically catheterized ovine fetuses and postnatal lambs in which growth restriction was induced during late gestation by embolizing the umbilico–placental vascular bed, a technique that replicates key aspects of human placental insufficiency.

5. During late gestation, restricting the growth of the ovine fetus did not alter lung weight or lung liquid secretion or volume when each factor was related to bodyweight, but it did lead to increased lung DNA concentrations and an increased thickness of the air–blood barrier. Expression of pulmonary surfactant proteins A, B and C were not altered and, hence, it was unlikely that surfactant protein synthesis had been impaired by growth restriction.

6. When growth restriction continued to term, lambs were born with a low birthweight and remained small compared with controls for 8 weeks after birth. Low‐birthweight lambs were mildy hypoxaemic and compliances of their lungs and chest wall were, respectively, decreased and increased relative to controls. Pulmonary surfactant proteins A, B and C were not deficient, indicating that decreased lung compliance most likely had a structural basis.

7. Morphometric analysis of lungs at 8 weeks after birth indicated that low‐birthweight lambs had increased alveolar wall thicknesses, less ‘air‐space’ and thicker blood–air barriers. These properties would be expected to restrict pulmonary gas exchange and decrease pulmonary compliance.

8. We conclude that growth restriction during early development can have lasting adverse effects on the lungs and chest wall and that these may be sufficient to affect respiratory function throughout later life as well as advancing ageing of the lungs.
Experimental Biology 2000 Symposium on Differential Control of Sympathetic Outflow DIFFERENTIAL PATTERNS OF SYMPATHETIC RESPONSES TO SELECTIVE STIMULATION OF NUCLEUS TRACTUS SOLITARIUS PURINERGIC RECEPTOR SUBTYPES
Authors: Scislo Tadeusz J , Kitchen Amy M , Augustyniak Robert A , O'Leary Donal S
Published: March 2003

1. Studies are described that indicate that stimulation of different purinergic receptor subtypes (A1, A2A and P2X) located in the sub‐postremal nucleus tractus solitarius (NTS) evokes qualitatively and quantitatively different regional haemodynamic and efferent sympathetic responses.

2. Stimulation of A2A receptors evoked the most diverse pattern of regional sympathetic responses: preganglionic adrenal nerve activity (pre‐ASNA) was increased, lumbar sympathetic nerve activity (LSNA) did not change, while renal (RSNA) and post‐ganglionic adrenal (post‐ASNA) sympathetic nerve activity was decreased. Stimulation of A1 receptors evoked qualitatively uniform, although quantitatively different, sympathoactivation: ↑pre‐ASNA > ↑RSNA >↑LSNA. Stimulation of P2X receptors evoked qualitatively uniform, although quantitatively different, sympathoinhibition: ↓RSNA = ↓post‐ASNA > ↓LSNA = ↓pre‐ASNA.

3. These qualitatively and quantitatively different patterns of regional sympathetic responses strongly suggest that purinergic receptor subtypes may be specifically located and differentially expressed on NTS neurons/neural terminals that control different sympathetic outputs. Different NTS purinoceptors may contribute to patterned autonomic responses observed in specific physiological or pathological situations.