bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraoperative lymph node staging of prostate cancer: the case against
Authors: Garrett Kerry L. , McNeal John E. , Cohen Ronald J.
Published: May 2003

Background:  Intraoperative frozen section analysis of obturator nodes is an accepted screening procedure, excluding from prostatectomy that group of node‐positive patients who are presumed to almost always have disseminated cancer. The overall efficacy of this procedure depends not only on the near inevitability of cancer progression in these patients, but also the procedure morbidity (previously estimated at 8.4%), the additional costs (currently estimated at A$1200) and the infrequency of positive nodes. We evaluate the efficacy of lymph node staging for prostate cancer.

Methods:  We have evaluated the efficacy of intraoperative screening by node dissection in 123 prostatectomy cases. These cases were prescreened from a series of 261 radical prostatectomies by evaluating preoperative serum PSA and Gleason grade.

Results:  Three patients were identified with nodal disease, representing a detection rate of 2.4%. The present study confirms that current trends in prostate cancer identification and selection of individuals for radical surgery very rarely identify node‐positive disease even after preselection with accepted ‘high‐risk’ markers.

Conclusion:  Considering the attendant cost and morbidity, there appears to be no justification for lymph node dissection as a routine preliminary to prostatectomy.
In vitro comparison of glyceryl trinitrate‐verapamil with other dilators of human saphenous vein
Authors: Jesuthasan L. S. Bruno , Angus James A. , Rosenfeldt Franklin L.
Published: May 2003

Background:  A common problem encountered during harvesting of the saphenous vein for coronary artery bypass grafting (CABG) is spasm of the vein. The previous work of the present authors has led to the development of a dilator solution containing glyceryl trinitrate (GTN) and verapamil for use during harvesting of the saphenous vein (SV) and the internal mammary artery. The present organ bath study was designed (i) to determine the best vasodilator agents for the saphenous vein during harvesting and (ii) to investigate the presence of any synergistic effect when vasodilator agents are combined.

Methods:  Discarded segments of saphenous vein were collected from 46 patients undergoing CABG and studied in organ baths. Initially veins were contracted with potassium or thromboxane A2 mimetic (U46619). Dilators were added individually or in com­bination in clinically relevant concentrations to study time of onset and maximum effect. The vasodilator agents tested included GTN, verapamil (V), sodium nitroprusside (SNP) and nicorandil (N).

Results:  When rapidity of onset (i.e. relaxation caused in the first minute) was considered, GTN or combinations containing GTN, caused a response that was significantly faster than the other vasodilators (P < 0.05). The maximum response caused by the GTN−V combination (61.4 ± 9.6%) was significantly greater than all the other single dilators, SNP (35 ± 4%) and N (10 ± 3%) (P < 0.05). However, no synergistic effects were demonstrated.

Conclusions:  The present paper demonstrates the following conclusions: (i) glyceryl trinitrate is a rapidly acting dilator of the human isolated SV. (ii) GTN−V combination is a potent combination causing a maximum dilator effect that is significantly greater than single agents including SNP and N.
Day‐only laparoscopic cholecystectomy in a regional teaching hospital
Authors: Blatt Alison , Chen Stanley
Published: May 2003

Background:  Day‐only laparoscopic cholecystectomy (DOLC) has been demonstrated to be a safe and feasible procedure. The aim of the present study was to introduce DOLC to a busy teaching hospital without a separate day‐surgery facility, to identify any problems associated with early discharge, and to determine patient satisfaction.

Methods:  Over a 2‐year period, all patients undergoing elective laparoscopic cholecystectomy under one surgeon were prospectively studied. Patients satisfying criteria for DOLC were offered the procedure. All patients were sent anonymous satisfaction surveys postoperatively.

Results:  One hundred and one patients underwent elective laparoscopic cholecystectomies and 41 of these patients were booked for DOLC. Thirty‐three (80%) were successfully discharged the same day and there were no complications related to early discharge. Only two of eight unplanned admissions were because of postoperative pain or nausea. Thirty‐two (78%) of DOLC patients replied to our survey and of those, 24 (78%) were satisfied with their length of stay. The extra strain placed on day‐stay ward resources was reflected in patient survey comments on their care.

Conclusions:  Our findings support the evidence that DOLC is safe and feasible. However, in a busy teaching hospital with tight budget constraints and no separate day‐surgery facility we found many patients satisfied with their length of stay but not always with the quality of care they received on the day‐stay ward. The latter was insufficiently equipped to handle procedures of this complexity. So although in theory DOLC has many advantages, we are unable to institute this as routine practice at this time.
Testicular microlithiasis: a case report and review of the literature
Authors: Lawrentschuk Nathan , Brough Stephen J. S. , De Ryke Rex J.
Published: May 2003

Testicular microlithiasis (TM) is a rare condition in which men have innumerable testicular calcifications. It is increasingly being reported on ultrasound. The published literature has reported an association between confirmed testicular malignancy and testicular microlithiasis. The relationship between TM and the risk of developing malignancy is unclear. The present paper reports a patient with a previously normal scrotal ultrasound except for bilateral sonographically detected TM who developed a testicular tumour. It also discusses the appropriate management of TM after reviewing the published literature.
Spinal and spinal cord injuries in horse riding: the New South Wales experience 1976−1996
Authors: Roe Justin P. , Taylor Thomas K. F. , Edmunds Ian A. , Cumming Robert G. , Ruff Stephen J. , Plunkett‐Cole Meg D. , Mikk Marje , Jones Richard F.
Published: May 2003

Objectives:  The objective of the present study was to determine the incidence of acute spinal cord injuries (ASCI) in all forms of horse riding in New South Wales (NSW) for the period 1976−1996. Other aims of the present study were to compare and contrast ASCI with vertebral column injuries (VCI) without neurological damage and to define appropriate safety measures in relation to spinal injury in horse‐riding.

Design:  A retrospective review was done of all ASCI cases (n = 32) admitted to the two acute spinal cord injury units in NSW for the cited period. A comparable review of VCI cases (n = 30) admitted to these centres for the period 1987−1995 was also undertaken.

Results:  A fall in flight was the commonest mode of injury in both groups. Occupational and leisure riding accounted for 88% of ASCI and VCI. The incidence of ASCI is very low in those riding under the aegis of the Equestrian Federation of Australia − two cases in 21 years; and there were no cases in the Pony Club Riders or in Riding for the Disabled. The difference in the spinal damage caused by ASCI and VCI is in degree rather than kind. Associated appendicular/visceral injuries were common.

Conclusions:  No measures were defined to improve spinal safety in any form of horse riding. The possible role of body protectors warrants formal evaluation. Continued safety education for all horse riders is strongly recommended.
Current attitudes to total hip replacement in younger patients: a comparison of two nations
Authors: Hardidge Andrew J. , Hooper Jonathan , McMahon Stephen
Published: May 2003

Introduction:  Orthopaedic surgeons performing total hip replacements (THR) today are faced with a vast array of options. Inspired by a recent UK study, we wanted to determine the current trend in prosthesis choice, fixation and bearing surfaces used in ‘young’ Australian patients, and to compare this trend to the UK.

Methods:  A questionnaire identical to that used in the UK study was posted to all current members of the Australian Orthopaedic Association and returned questionnaires were directly compared to the UK results on a percentage‐of‐responses basis.

Results:  Two hundred and forty‐six valid responses were received. The number of THR reported to be performed by these respondents (15 789) was equivalent to the estimated number of prostheses sold here during the same period (15 624). The UK results showed a predominant use of Charnley and Exeter femoral prostheses, an all‐polyethylene acetabular component, and cement fixation of both the acetabular and femoral components for both their older and younger patients. In younger patients, Australian surgeons favoured uncemented fixation techniques for the femur (57%vs 23%), and especially the acetabulum (85%vs 32%). There was a higher percentage use of modular design (95%vs 67%) and a very high use of ceramic as a bearing surface, 49% (vs 25%) using it for the femoral head, and 21% (vs 2%) employing a ceramic‐on‐ceramic bearing combination.

Discussion:  Despite being privy to the same published papers, the THR prosthesis and fixation preferences of UK and Australian orthopaedic surgeons are markedly different. This may be because of interpretation of papers, peers, personal experience, patient assessment, budgets, institutions, theories, fashions, differences in autonomy and advertising.
Embryonic parathyroid rests occur commonly and have implications in the management of secondary hyperparathyroidism
Authors: Aly Ahmad , Douglas Malcolm
Published: May 2003

Background:  Recurrence after surgery for secondary hyperparathyroidism is not infrequent. Regrowth of the residual parathyroid tissue after subtotal parathyroidectomy or of the autograft after total parathyroidectomy occurs in many cases. Supernumerary glands are also frequently cited as the offending cause and upon revisiting the neck, the surgeon may be surprised that such an obvious gland was ‘missed’ at the first operation. Indeed, multiple glands removed in sequential operations have been reported suggesting that they develop over time rather than being present from the start. It is possible that microscopic parathyroid ‘rests’ of embryological origin proliferate under the ongoing stimulus of renal failure to produce supernumerary glands after apparently adequate initial surgery for hyperparathyroidism. The aim of the present study was to determine whether such rests occur frequently or infrequently.

Methods:  Operative details and pathology results from 60 consecutive parathyroidectomies were reviewed and the occurrence of parathyroid rests noted.

Results:  Parathyroid rests were found in 37% of extra parathyroidal tissues submitted for analysis. These rests were found commonly in the thymus. The potential significance of such parathyroid rests undergoing hyperplasia in response to the ongoing stimulus of renal failure and leading to recurrent hyperparathyroidism is discussed.

Conclusion:  Parathyroid rests are common and potentially serve as a cause of recurrent disease in secondary hyperparathyroidism. Consideration should be given to performing thymectomy as part of the treatment of secondary hyperparathyroidism. A more detailed study is warranted.
Men with colorectal cancer are predisposed to prostate cancer
Authors: Moot Andrew R. , Polglase Adrian , Giles Graham G. , Garson O. Margaret , Thursfield Vicky , Gunter David
Published: May 2003

Background:  The objective of the present study was to investigate the relationship between colorectal and prostate cancer.

Methods:  All Victorian men who developed metachronous colorectal and prostate cancer with the first primary diagnosed between 1982 and 1993 were identified retrospectively from the Victorian Cancer Registry and were followed up to the end of 1995. Analyses were stratified by age group and years of follow up. The cause of death in those men who had prostate cancer following colorectal cancer was determined. The stage of colorectal cancer was compared between men with and without second primary prostate cancer and the grade of prostate cancer was compared with men who did not have a prior colorectal cancer.

Results:  Men who develop colorectal cancer are at increased risk of prostate cancer, with the greatest risk in men under the age of 65 (Relative risk ∼2). Men with first primary colorectal cancer are more likely to develop prostate cancer than colorectal second primaries, and men who develop second primary prostate cancer are more likely to die of prostate cancer than colorectal cancer.

Conclusions:  Younger men diagnosed with colorectal cancer are at increased risk of prostate cancer. However, there is no direct evidence that screening for prostate cancer leads to a reduction in mortality. This should be considered when discussing long‐term follow up.
Radical lymph node dissection for melanoma
Authors: Serpell Jonathan W. , Carne Peter W. G. , Bailey Michael
Published: May 2003

Background:  Therapeutic lymph node dissection for melanoma aims to achieve regional disease control. Radical lymphadenectomy (RLND) can be a difficult procedure associated with significant postoperative morbidity.

The aims of the present study were to review regional disease control and morbidity in a series of lymphadenectomies performed within a specialist unit.

Methods:  The present study involved the analysis of 73 lymphadenectomies in 64 patients, from 1995 to 2001.

Results:  The overall wound complication rate after inguinal lymphadenectomy (71%) was higher than after axillary lymphadenectomy (47%; P = 0.05). After inguinal lymphadenectomy, the wound infection rate was higher (25.0%vs 5.9%; P = 0.03), delayed wound healing was more frequent (25.0%vs 5.9%; P = 0.03), and the mean time that drain tubes remained in situ was longer (12.5 vs 8.2 days; P = 0.05). There were no significant differences in seroma (46%vs 32%) rates. Lymphoedema was more common after inguinal lymphadenectomy (P < 0.02). Multivariate analysis identified inguinal RLND (P = 0.002) and increasing tumour size (P = 0.045) as predictors of wound morbidity. More patients received postoperative radiotherapy after neck RLND compared to inguinal or axilla RLND (P = 0.03). Six (8%) patients developed local recurrence after lymphadenectomy. At a median follow up of 22 months, 34 (53%) patients have died, from disseminated disease.

Conclusions:  Radical lymphadenectomy for melanoma is associated with significant morbidity. Inguinal node dissection has a higher rate of complications than axillary dissection. Low local recurrence rates can be achieved, limiting the potential morbidity of uncontrolled regional metastatic disease.
Biliary access loops for intrahepatic stones: results of jejunoduodenal anastomosis
Authors: Ramesh Hariharan , Prakash Kurumboor , Kuruvilla Kuruvilla , Philip Mathew , Jacob George , Venugopal B. , Lekha V. , Varma Deepak
Published: May 2003

Background:  Patients with intrahepatic calculi require multiple interventions following successful surgical stone clearance for recurrent stones and cholangitis. The present paper describes the results of a technique of in‐continuity side‐to‐side jejunoduodenal anastomosis (JDA) that provides endoscopic access to the hepaticojejunostomy and intrahepatic ducts. This operation is compared to other techniques in a critical appraisal of various biliary access procedures described for long‐term management of intrahepatic ­calculi.

Methods:  A retrospective analysis of clinical data of 13 patients who underwent biliary drainage procedures with access loops for intrahepatic calculi during the period March 1990 to December 2000 was performed. The postoperative course of patients and the feasibility of postoperative endoscopic access to the hepaticojejunostomy and intrahepatic ductal system in treatment of recurrent cholangitis were assessed. Nine patients underwent JDA, two underwent permanent‐access hepaticojejunostomy (PAH) and two others underwent an interposition hepaticojejunoduodenostomy (IHJ).

Results:  The analysis revealed no major procedure‐related complications or mortality. Endoscopic access (using forward‐viewing gastroscope) was possible in 100% of cases following JDA, and with difficulty in both cases after PAH. Endoscopic access in the two patients with IHJ failed because of technical reasons. Recurrent cholangitis was seen in seven patients (54%) − two out of two patients in the PAH group, one out of two in the IHJ group and four out of nine in the JDA group. This required 12 endotherapy sessions (mean: 1.5 procedures per patient).

Conclusion:  In‐continuity side‐to‐side JDA allows easy access of conventional gastroduodenoscopes to the biliary tree for removal of recurrent/residual intrahepatic stones. The technique has advantages over other access loop procedures in the long term management of recurrent intrahepatic stones.
Pierre Dionis and the Franco−British dialogue in surgery
Authors: Simpson Donald
Published: May 2003

Pierre Dionis (1643?−1718), though not himself a very innovative surgeon, has been acclaimed as the author of a surgical textbook that opened a new era in which French surgical teaching dominated Europe. This dominance is reflected in the Gordon Craig Library, which contains four copies of the book by Dionis in English translation, as well as a number of other books by influential French 18th century surgical writers, notably Henri François Le Dran and François Quesnay. It is significant that many of these writers benefited from government patronage in various forms. Dionis himself began his career as demonstrator in anatomy and surgery at the Jardin du Roi, in his time the premier teaching institution in those sciences. He later became a court surgeon.

 During the course of the 18th century, French surgery gained ascendancy over French academic medicine and also on the inter­national stage. English surgery, likewise, made great progress. There was a very productive dialogue between medical scientists and teachers in both countries, assisted by textbooks in translation.

 The French Revolution demolished the medical and surgical institutions established under the old regime, but French surgery emerged from the rubble to play a great part in the birth of modern clinical medicine
Intrinsic light responses of retinal ganglion cells projecting to the circadian system
Authors: Warren Erin J. , Allen Charles N. , Brown R. Lane , Robinson David W.
Published: May 2003

In mammals, light entrainment of the circadian clock, located in the suprachiasmatic nuclei (SCN), requires retinal input. Traditional rod and cone photoreceptors, however, are not required. Instead, the SCN‐projecting retinal ganglion cells (RGCs) function as autonomous photoreceptors and exhibit light responses independent of rod‐ and cone‐driven input. Using whole‐cell patch‐clamp recording techniques, we have investigated the morphological and electrophysiological properties of this unique class of RGCs. Although SCN‐projecting RGCs resemble Type III cells in form, they display strikingly different physiological properties from these neurons. First, in response to the injection of a sustained depolarizing current, SCN‐projecting cells fired in a transient fashion, in contrast to most RGCs which fired robust trains of action potentials. Second, in response to light, SCN‐projecting RGCs exhibited an intensity‐dependent transient depolarization in the absence of rod and cone input. This depolarization reached a peak within 5 s and generated increased spiking activity before decaying to a plateau. Voltage‐clamp recordings were used to characterize the light‐activated conductance which generated this depolarization. In response to varying light intensities, SCN‐projecting RGCs exhibited a graded transient inward current which peaked within 5 s and decayed to a plateau. The voltage dependence of the light‐activated current was obtained by subtracting currents elicited by a voltage ramp before and during illumination. The light‐activated current displayed both inward and outward rectification and was largely unaffected by substitution of extracellular Na+ with choline. In both respects, the intrinsic light‐activated current observed in SCN‐projecting RGCs resembles currents carried by ion channels of the transient receptor potential (trp) family, which are known to mediate the light response of invertebrate photoreceptors.
Ontogenetic development of cannabinoid receptor expression and signal transduction functionality in the human brain
Authors: Mato Susana , Del Olmo Elena , Pazos Angel
Published: May 2003

Previous evidence suggests that the endogenous cannabinoid system emerges relatively early during brain development in the rat. However, the pre‐ and postnatal pattern of appearance of CB1 cannabinoid receptors in humans has not been analysed in detail. Furthermore, there is a complete lack of information about the functional ability of these proteins to activate signal transduction mechanisms during human development. In the present study we have explored CB1 receptor expression throughout the different areas of the developing human brain by [3H]CP55 940 autoradiography. We have also assessed CB1 functional coupling to G proteins during brain development by agonist‐stimulated [35S]GTPγS autoradiography in the same cases. Our results indicate a significant density of cannabinoid receptors at 19 weeks' gestation in the same areas that contain these receptors in the adult human brain. Autoradiographic levels of CB1 receptors in these structures seem to increase progressively from early prenatal stages to adulthood. Interestingly, high densities of cannabinoid receptors have also been detected during prenatal development in fibre‐enriched areas that are practically devoid of them in the adult brain. In parallel with these data, we have found that brain cannabinoid receptors are functionally coupled to signal transduction mechanisms from early prenatal stages. This early pattern of expression of functionally active cannabinoid receptors, along with the transient and atypical localization of these proteins in white matter areas during the prenatal stages, suggest an specific role of the endocannabinoid system in the events related to human neural development.
Neurokinin 1 receptor and relative abundance of the short and long isoforms in the human brain
Authors: Caberlotto Laura , Hurd Yasmin L. , Murdock Paul , Wahlin Jean Philippe , Melotto Sergio , Corsi Mauro , Carletti Renzo
Published: May 2003

Substance P exerts its various biochemical effects mainly via interactions through neurokinin‐1 receptors (NK1). Recently, the NK1 receptor has attracted considerable interest for its possible role in a variety of psychiatric disorders including depression and anxiety. However, little is known regarding the anatomical distribution of NK1 in the human central nervous system (CNS). Riboprobe in situ hybridization, quantitative PCR and in vitro autoradiography were performed. Highest NK1 mRNA levels were localized in the locus coeruleus and ventral striatum, while moderate hybridization signals were observed in the cerebral cortex (most abundant in the visual cortex), hippocampus and different amygdaloid nuclei. Very low levels of the NK1 mRNA were detected in the cerebellum and thalamus. In view of the existence of a long and short isoform of the NK1 receptor, it was of interest to assess whether there was a differential distribution of the two splice variants in the human CNS and peripheral tissues. A quantitative TaqMan PCR analysis showed that the long NK1 isoform was the most prevalent throughout the human brain, while in peripheral tissues the truncated form was the most represented. 3H‐Substance P autoradiography revealed a good correlation between receptor binding sites and NK1 mRNA expression throughout the brain, with the highest levels of binding in the locus coeruleus. These results provide the anatomical evidence that the NK1 receptors have a strong association with neuronal systems relevant to mood regulation and stress in the human brain, but do not suggest a region‐specific role of the two isoforms in the CNS.
Interhemispheric visuo‐motor integration in humans: the effect of redundant targets
Authors: Iacoboni Marco , Zaidel Eran
Published: May 2003

We used event‐related functional magnetic resonance imaging (fMRI) to investigate the functional locus of response facilitation during parallel visuo‐motor processing. In a simple reaction‐time task, subjects typically respond faster to two copies of the same stimulus than to a single copy. This facilitation, called the redundant‐target effect, can occur at three functional levels: perceptual, ‘cognitive’ or motor. Normal right handers were studied while performing a simple reaction‐time task to unilateral (left or right) and bilateral light flashes. Subjects were instructed to respond with their right index finger. Reaction times were faster to bilateral light flashes than to unilateral ones, even right flashes. Greater fMRI signal for bilateral stimuli compared to unilateral ones was observed in the left precentral and postcentral gyrus, and in the right precentral gyrus. A greater fMRI signal for bilateral and for unilateral left stimuli, compared to unilateral right stimuli, was observed in an area of the right intraparietal sulcus. These results support the hypothesis that the functional locus of response facilitation during parallel visuo‐motor processing is premotor.
Blockade of nociceptin/orphanin FQ–NOP receptor signalling produces antidepressant‐like effects: pharmacological and genetic evidences from the mouse forced swimming test
Authors: Gavioli E. C. , Marzola G. , Guerrini R. , Bertorelli R. , Zucchini S. , De Lima T. C. M , Rae G. A. , Salvadori S. , Regoli D. , Calo G.
Published: May 2003

Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the NOP receptor, regulates several central functions such as pain transmission, learning and memory, fear and anxiety and feeding and locomotor activity. It has been recently reported that NOP receptor antagonists induce antidepressant‐like effects in the mouse forced swimming test (FST), i.e. reduce immobility time. This assay was used in the present study for further investigating the involvement of the NOP receptor in depression states. In male Swiss mice, intracerebroventricular injection (i.c.v) of the novel NOP receptor antagonist, UFP‐101 (1–10 nmol) dose‐dependently reduced the immobility time (control 192 ± 14 s, UFP‐101 91 ± 15 s). The effect of 3 or 10 nmol UFP‐101 was fully or partially reversed, respectively, by the coadministration of 1 nmol N/OFQ, which was inactive per se. NOP receptor knockout mice showed a reduced immobility time compared with their wild‐type littermates (wild‐type 215 ± 10 s, knockout 143 ± 12 s). Moreover, i.c.v. injected UFP‐101 (10 nmol) significantly reduced immobility time in wild‐type mice but not in NOP receptor knockout animals. In conclusion, these results, obtained using a combined pharmacological and genetic approach, indicate that blockade of the N/OFQ‐NOP receptor signalling in the brain produces antidepressant‐like effects in the mouse FST. These findings support the NOP receptor as a candidate target for the development of innovative antidepressant drugs.
Enzymatic removal of chondroitin sulphates abolishes the age‐related axon order in the optic tract of mouse embryos
Authors: Leung Kim‐Mei , Taylor Jeremy S. H. , Chan Sun‐On
Published: May 2003

Retinal axons undergo an age‐related reorganization at the junction of the chiasm and the optic tract. We have investigated the effects of removal of chondroitin sulphate on this order change in mouse embryos aged embryonic day 14, when most axons are growing in the optic tract. Enzymatic removal of chondroitin sulphate but not keratan sulphate in brain slice preparations of the retinofugal pathway abolished the accumulation of phalloidin‐positive growth cones in the subpial region of the optic tract. The loss of chronotopicity was further demonstrated by anterograde filling of single retinal axons, which showed a dispersion of growth cones from subpial to the whole depth of the tract. The enzyme treatment neither produced detectable changes in growth cone morphology and growth dynamic of retinal neurites nor affected the radial glial processes in the tract, indicating a specific effect of removal of chondroitin sulphate from the pathway to the axon order in the tract. Although chondroitin sulphate was also found at the midline of the chiasm, growth cone distribution across the depth of fibre layer at the midline was not affected by the enzyme treatment. These results suggest a mechanism in which retinal axons undergo changes in response to chondroitin sulphate at the chiasm–tract junction, but not at the midline, that produce a chronotopic fibre rearrangement in the mouse retinofugal pathway.
γ‐Frequency fluctuations of the membrane potential and response selectivity in visual cortical neurons
Authors: Volgushev Maxim , Pernberg Joachim , Eysel Ulf T.
Published: May 2003

Fluctuations at frequencies of 25–70 Hz is an inherent property of cortical activity. These rapid, γ‐range fluctuations are apparent in the local field potentials, in spiking of cells and cell groups, and in the membrane potential of neurons. To investigate stimulus dependence of the γ‐frequency fluctuations of the membrane potential, we have recorded intracellularly responses of cells in cat visual cortex to presentation of moving gratings. We found γ‐range fluctuations of the membrane potential in both simple and complex cells. The strength of the γ‐frequency fluctuations correlated with the stimulus optimality. Furthermore, the amplitude of the γ‐frequency fluctuations correlated with the phase of stimulus‐imposed slow changes of the membrane potential. The combination of these features makes cortical neurons capable of encoding the slow changes in the visual world in a kind of amplitude modulation of the high frequency fluctuations. This assures reliable transformation of the membrane potential changes into spike responses without compromising the temporal resolution of visual information encoding in the low frequency range.
Learning deficits and dysfunctional synaptic plasticity induced by aggregated amyloid deposits in the dentate gyrus are rescued by chronic treatment with indomethacin
Authors: Stéphan Aline , Laroche Serge , Davis Sabrina
Published: May 2003

The amyloid pathology in Alzheimer's disease is accompanied by a chronic inflammatory response characterized by gliosis and activated microglial cells surrounding senile plaques. Epidemiological studies have shown nonsteroidal anti‐inflammatory drug treatment reduces the risk of Alzheimer's disease. We have previously shown that injection of a combination of Aβ40 and Aβ43 in the dentate gyrus of the rat induces aggregated amyloid deposits and inflammation associated with dysfunctional synaptic plasticity and learning deficits. Here we characterize the effectiveness of nonsteroidal anti‐inflammatory treatment in this model and show that this treatment restores the working memory deficit and decremental long‐term potentiation in the dentate gyrus. Importantly, we observe no qualitative difference in the presence of aggregated material but a substantial reduction in microglial‐induced inflammation, suggesting that mature aggregated plaques may not be directly responsible for the deficits but may trigger an inflammatory response which has a detrimental effect on synaptic function and memory.
Modulation of GABAergic transmission by endogenous glutamate in the rat supraoptic nucleus
Authors: Piet Richard , Bonhomme Renée , Theodosis Dionysia T. , Poulain Dominique A. , Oliet Stéphane H. R.
Published: May 2003

The presence of group III metabotropic glutamate receptors on GABAergic terminals in the supraoptic nucleus suggests that the level of glutamate in the extracellular space may regulate synaptic strength at inhibitory synapses. To test this hypothesis we examined the consequences of increasing ambient glutamate on GABA‐mediated synaptic activity in supraoptic neurons. The concentration of the excitatory amino acid in the extracellular space was increased pharmacologically by blocking glutamate transporters. Inhibition of the astrocyte‐specific GLT‐1 glutamate transporter led to a reversible decrease in evoked inhibitory postsynaptic current amplitude. This modulation had a presynaptic origin as revealed by analysis of paired‐pulse ratio and miniature inhibitory currents. Furthermore, blocking group III metabotropic glutamate receptors with the specific antagonist MAP4 prevented the depression of GABAergic transmission induced by glutamate transporter blockade. Thus, presynaptic metabotropic glutamate receptors located on inhibitory terminals in the supraoptic nucleus appear to sense changes in ambient glutamate and modify GABA release accordingly. However, it seems that such changes need to reach a certain magnitude because the discrete deficit in glutamate clearance which occurs in the supraoptic nucleus of lactating rats is not sufficient to modulate GABA‐mediated transmission. These results suggest that ambient glutamate contributes to the modulation of synaptic efficacy not only at glutamatergic synapses but also at inhibitory GABAergic synapses.
Effect of sleep and sleep deprivation on serotonergic neurotransmission in the hippocampus: a combined in vivo microdialysis/EEG study in rats
Authors: Peñalva Rosana G. , Lancel Marike , Flachskamm Cornelia , Reul Johannes M. H. M. , Holsboer Florian , Linthorst Astrid C. E.
Published: May 2003

Brainstem serotonergic neurotransmission is implicated in sleep regulation. However, the role of serotonin (5‐HT) in forebrain regions in sleep–wake mechanisms is still unclear. Here, we have investigated, using a combined in vivo microdialysis/electroencephalogram method, the relationship between hippocampal 5‐HT levels and sleep–wake behaviour in the rat. A clear‐cut relationship was found between hippocampal 5‐HT levels and vigilance state. The highest levels of 5‐HT were observed during wakefulness, whereas a progressive decrease of 5‐HT going from nonrapid eye movement sleep to rapid eye movement sleep was found. Sleep deprivation (SD) causes a transient enhancement of mood in depressed patients. Given the putative role of 5‐HT in the aetiology of depression and the therapeutical efficacy of selective serotonin reuptake inhibitors in this illness, we also studied hippocampal 5‐HT during 4 h of SD and during the subsequent recovery period. During the whole SD period, 5‐HT levels were elevated substantially when compared to 5‐HT levels during basal wakefulness. However, no changes in 5‐HT levels and the relationship between hippocampal 5‐HT and vigilance state were found during the subsequent recovery period. As SD is a potentially stressful experience and glucocorticoids are involved in the regulation of serotonergic neurotransmission and sleep, we investigated the effects of SD on free corticosterone levels. SD caused a marked rise in free corticosterone levels. However, the effects of SD on 5‐HT seem not to be mediated by this hormone, because adrenalectomy did not affect the rise in hippocampal 5‐HT during SD. We hypothesize that the elevated hippocampal 5‐HT levels during SD may participate in the transient mood enhancing properties of forced wakefulness observed in depressed patients.
Evidence for a function‐specific mutation in the neurotoxin, parabutoxin 3
Authors: Huys Isabelle , Tytgat Jan
Published: May 2003

Parabutoxin 3 (PBTx3), a short‐chain α‐K+ neurotoxin from the scorpion, Parabuthus transvaalicus, is a 37‐residue polypeptide cross‐linked by three disulphide bridges. The affinity towards Kv1 channels is very weak (Kd ≈ 79 µm for Kv1.1 channels), or moderate (Kd ≈ 500 nm for Kv1.2 and Kv1.3 channels). In an effort to generate a more potent K+ channel blocker, we recombinantly produced a mutant PBTx3 by the introduction of an aromatic amino acid, fenylalanine in close proximity of the crucial lysine 26 residue, to create a functional diad similar to subfamily three α‐K+ toxins. The mutant was tested for his ability to block Kv1.1, Kv1.2 and Kv1.3 channels in Xenopus laevis oocytes: a hundred‐fold higher affinity towards Kv1.1 channels and a fivefold increase in affinity towards Kv1.3 channels was observed, when compared to the wild‐type toxin. The effect on Kv1.2 channels was similar to the wild‐type toxin, indicating a specific interaction site for the mutated residue onto the different Kv‐type channels.
The effects of ibotenic hippocampal lesions on discriminative fear conditioning to context in mice: impairment or facilitation depending on the associative value of a phasic explicit cue
Authors: Desmedt Aline , Marighetto Aline , Garcia René , Jaffard Robert
Published: May 2003

To what extent the hippocampus is required for contextual conditioning remains a matter of debate. The present experiments examined the effects of ibotenate hippocampal lesions on discriminative fear conditioning to context in mice using measures of freezing in two conditioning paradigms. In both paradigms animals received foot shock as the unconditional stimulus (US) when placed in the (conditioning) context and no foot‐shock when placed in the other (neutral) context. In both contexts, animals were presented with a tone as the conditioned stimulus (CS). In the conditioning context there was either no interval (delay condition) or a 30‐s interval (trace condition) between tone CS end and shock US onset. These two paradigms were used because theory predicts that in the trace condition animals would learn more about contextual cues as predictors, or not, of shock US occurrence than in the delay condition. In agreement with this, we observed that sham‐operated mice learned the context discrimination faster in the trace than in the delay condition. Lesions of the hippocampus significantly retarded, but did not prevent, the acquisition of the context discrimination in the trace condition. In contrast, lesions produced an opposite (facilitatory) effect in the delay condition, which was mainly observed during tone CS presentation. The data suggest that mice used two distinct competing strategies in solving this discrimination task: (i) a strategy relying on the processing of background contextual stimuli allowing direct establishment of context–US associations of different strengths, and (ii) a conditional cue (tone)‐based strategy. Hence, hippocampal lesions may impair the use of the former strategy while exacerbating (unmasking) the use of the latter.
Melanopsin retinal ganglion cells and the maintenance of circadian and pupillary responses to light in aged rodless/coneless (rd/rd cl) mice
Authors: Semo Ma'ayan , Peirson Stuart , Lupi Daniela , Lucas Robert J. , Jeffery Glen , Foster Russell G.
Published: May 2003

Melanopsin‐expressing ganglion cells have been proposed as the photoreceptors mediating non‐rod, non‐cone ocular responses to light. Here we use the aged (approximately 2 years) rodless and coneless (rd/rd cl) mouse to assess the impact of progressive inner retinal cell loss on melanopsin expression, circadian entrainment and pupillary constriction. Aged rd/rd cl mice show substantial transneuronal retinal degeneration leaving only the ganglion cell layer and little of the inner nuclear layer. Despite this loss, quantitative reverse transcriptase‐polymerase chain reaction showed normal levels of melanopsin expression, and immunocytochemistry demonstrated both the presence and normal cellular appearance of these cells. Furthermore, the optic nerves of the two genotypes (rd/rd cl and +/+) were not obviously different in animals older than 2 years. However, this massive level of retinal degeneration left both pupillary and circadian responses to light intact, even in rd/rd cl mice older than 2 years. Our data provide the first positive correlation between the persistence of melanopsin‐expressing cells and the maintenance of both circadian and pupillary responses to light in the absence of rods and cones. These findings, together with recent studies on melanopsin knockout mice, are consistent with the hypothesis that melanopsin‐expressing ganglion cells are photosensitive and mediate a range of irradiance‐detection tasks.
Induction of the learning and plasticity‐associated gene Zif268 following exposure to a discrete cocaine‐associated stimulus
Authors: Thomas Kerrie L. , Arroyo Mercedes , Everitt Barry J.
Published: May 2003

We investigated whether the expression of the plasticity‐associated gene, zif268, was associated with memories retrieved by exposure to a discrete stimulus that had been associated with cocaine, either self‐administered or administered noncontingently. In the absence of drug, passive presentation of a cocaine‐associated light stimulus induced changes in the expression of zif268 measured by in situ hybridization within a limbic cortical–ventral striatal circuit that was not only regionally selective but related to whether the rats had originally received response‐contingent or noncontingent stimulus‐drug pairings. In rats that had self‐administered drug, the cocaine–conditioned stimulus (CS) increased zif268 expression in neurons of the ventral tegmental area, nucleus accumbens core and shell, and basal nucleus of the amygdala but not hippocampus, prelimbic area of the medial prefrontal cortex or amygdala central nucleus. The same CS that had been associated with cocaine administered noncontingently additionally increased zif268 mRNA levels in area Cg1 of the anterior cingulate cortex, ventral and lateral regions of the orbitofrontal cortex and lateral nucleus of the amygdala. Zif268 induction was related to the predictive relationship between the stimulus and cocaine as no changes were seen in cocaine‐experienced rats that had received unpaired light and drug presentations during training. Thus, zif268 expression is increased by appetitively (drug) conditioned stimuli after Pavlovian learning. Zif268 may participate in the molecular mechanisms underlying the reconsolidation or re‐encoding of Pavlovian stimulus–drug associations across a distributed limbic cortical‐ventral striatal neural network and that may contribute to the basis of the enduring drug‐seeking behaviour produced by environmental cues.
Regulation of α1G T‐type calcium channel gene (CACNA1G) expression during neuronal differentiation
Authors: Bertolesi Gabriel E. , Jollimore Christine A. B. , Shi Chanjuan , Elbaum Lindsy , Denovan‐Wright Eileen M. , Barnes Steven , Kelly Melanie E. M.
Published: May 2003

Down‐regulation of T‐type Ca channel current and mRNA occurs following differentiation of Y79 retinoblastoma cells. To understand how the decrease in expression is linked to cell differentiation, we examined transcriptional regulation of the Cav3.1 Ca channel gene, CACNA1G. We identified two putative promoters (A and B) in 1.3 kb of cloned genomic DNA. Reverse transcriptase‐polymerase chain reaction and 5′ rapid amplification of cDNA ends‐polymerase chain reaction analyses demonstrated that two transcripts with different 5′ untranslated regions are generated by different transcription start sites, with promoter A favoured in undifferentiated cells and promoter B favoured in differentiated cells. Functional analyses of the promoter sequence revealed that both promoters are active. Enhancer and repressor sequences were identified upstream of promoter A and B, respectively. These results suggest that the down‐regulation of α1G mRNA in differentiated Y79 cells is mediated primarily by decreased activity of promoter A, which could occur in conjunction with repression of the activity of promoter B. The decrease in T‐type Ca channel expression in Y79 cells may be an essential signal affecting phenotypic maturation and expression of other ion channel subtypes in the differentiated cells.
Rhythm sequence through the olfactory bulb layers during the time window of a respiratory cycle
Authors: Buonviso Nathalie , Amat Corine , Litaudon Philippe , Roux Stephane , Royet Jean‐Pierre , Farget Vincent , Sicard Gilles
Published: May 2003

The mammalian olfactory bulb is characterized by prominent oscillatory activity of its local field potentials. Breathing imposes the most important rhythm. Other rhythms have been described in the β‐ and γ‐frequency ranges. We recorded unitary activities in different bulbar layers simultaneously with local field potentials in order to examine the different relationships existing between (i) breathing and field potential oscillations, and (ii) breathing and spiking activity of different cell types. We show that, whatever the layer, odour‐induced γ oscillations always occur around the transition point between inhalation and exhalation while β oscillations appear during early exhalation and may extend up to the end of inhalation. By contrast, unitary activities exhibit different characteristics according to the layer. They vary in (i) their temporal relationship with respect to the respiratory cycle; (ii) their spike rates; (iii) their temporal patterns defined according to the respiratory cycle. The time window of a respiratory cycle might thus be split into three main epochs based on the deceleration of field potential rhythms (from γ to β oscillations) and a simultaneous gradient of spike discharge frequencies ranging from 180 to 30 Hz. We discuss the possibility that each rhythm could serve different functions as priming, gating or tuning for the bulbar network.
Deficit in long‐term contextual fear memory induced by blockade of β‐adrenoceptors in hippocampal CA1 region
Authors: Ji Jin‐Zhao , Wang Xin‐Ming , Li Bao‐Ming
Published: May 2003

The present study investigated the effects of intra‐CA1 infusion of d,l‐propranolol, the β‐adrenergic antagonist, on memory for contextual fear conditioning. d,l‐Propranolol administered 5 min (‘0 h’) postconditioning impaired long‐term but not short‐term contextual fear memory, while it was ineffective when administered 6 h postconditioning, suggesting that there is a time window for β‐adrenoceptors to play a role. Thus, we conclude that β‐adrenoceptors in area CA1 are involved in regulating consolidation of contextual fear memory, with ‘0 h’ but not 6 h post‐training, a sensitive time point for the β‐adrenergic involvement.
Impaired glutamate uptake and EAAT2 downregulation in an enterovirus chronically infected human glial cell line
Authors: Legay Vincent , Deleage Christelle , Beaulieux Frederik , Giraudon Pascale , Aymard Michelle , Lina Bruno
Published: May 2003

Rapid and efficient uptake of glutamate via the high‐affinity glutamate transporter EAAT2 is important for limiting glutamate‐mediated excitotoxicity involved in neuronal death. Furthermore, there is evidence of altered glutamate uptake and catabolism in motor neuron diseases. Such a defect has been reported in amyotrophic lateral sclerosis, the major motor neuron disease, and was associated with impairment in EAAT2 processing. We recently reported the presence of enterovirus genome specifically in the anterior horn of amyotrophic lateral sclerosis cases, suggesting the involvement of a chronic/persistent enterovirus infection in amyotrophic lateral sclerosis. To investigate a putative link between enterovirus infection and the glutamate‐mediated excitotoxicity observed in amyotrophic lateral sclerosis, we developed an in vitro model consisting of a human glial cell line infected with ECHOvirus 6, one of the enteroviruses with sequences closely related to those detected in patients with amyotrophic lateral sclerosis. In these glial cells, an ECHOvirus 6 chronic infection was established, resulting in altered extracellular glutamate uptake. This correlated with an aberrant splicing of the EAAT2 pre‐messenger ribonucleic acid and a significant loss of EAAT2 protein expression, similar to that observed in patients with amyotrophic lateral sclerosis. These results provide convincing evidence that an enterovirus chronic/persistent infection may alter glial glutamate uptake and catabolism. As enteroviruses are extremely common human pathogens, they may act as a trigger in the development of certain motor neuron diseases, such as amyotrophic lateral sclerosis.