Peripheral tuberculous lymphadenopathy: a review of 67 cases. Peripheral tuberculous lymphadenopathy is the commonest form of extrapulmonary tuberculosis. Sixty-seven patients with peripheral tuberculous lymphadenopathy who presented to general surgeons and underwent lymph node biopsy between 1979 and 1989 are reviewed. Fifty-four patients (81 per cent) were of Indian subcontinent ethnic origin and 13 (19 per cent) were of white ethnic origin. The sites most commonly affected were the cervical lymph nodes. Biopsy specimens obtained by open operation were sent for microbiological examination in all but 13 cases, of whom seven were patients of white ethnic origin. Tuberculous lymphadenopathy remains an important differential diagnosis of cervical lymphadenopathy and it is essential that peripheral lymph node biopsies are examined both histologically and microbiologically.


Subclinical injuries in lacerations to the forearm and hand. This report describes the incidence and severity of subclinical injuries to underlying structures in lacerations to the hand and forearm. One hundred consecutive hand and forearm lacerations that penetrated the full thickness of subcutaneous tissue were studied prospectively. Lacerations were explored under either biceps or forearm tourniquets. Injuries, treatment, tourniquet time, causative agent and complications were recorded. In all, 97 patients sustained 100 lacerations. A total of 49 deep injuries were discovered, none of which was detected clinically before exploration. Of these, 33 were tendon lacerations; 21 tendons, including three flexor tendons, were repaired. Nineteen patients required treatment in a volar slab for at least 3 weeks. Five patients of 49 returning for review developed wound infection. No patient developed significant problems related to the tourniquet, which was inflated for a mean time of 4.9 min. There is a high incidence of subclinical injury in full-thickness lacerations of the forearm and hand. These should be explored under tourniquet, which should minimize complications such as wound infection and delayed tendon rupture.


Parotid disease and human immunodeficiency virus infection in Zambia. Among the salivary glands the parotid is unusual in that it contains lymphoid tissue within its capsule. The focus of infection with human immunodeficiency virus (HIV) is the lymphatic system and this results in a specific HIV-related pathology in the parotid. This 2-year surgical audit of parotid disease in HIV-infected patients in Lusaka shows patients presenting with parotid lymphadenopathy, bilateral diffuse parotid enlargement and parotid lymphoepithelial cysts. Clinical presentation and management are discussed.


Breast cancer in Nigerian women.

Breast cancer in Nigerian women. A combined retrospective (1971-1980) and prospective (1981-1990) study of the epidemiology, clinical characteristics and pathology of breast cancer in a black African population was carried out. There were 1946 biopsy-proven cases, with a rate frequency of 33.6 per 100,000 patients per year. The age range was 14-96 years but 70 per cent of patients were between 26 and 50 years old. The cumulative frequency of cancer was 0.8 per cent at age < 20 years and 3.3 per cent at age < 25 years; the peak age range for disease was 36-45 years. Of 1842 evaluable patients, 17.2 per cent presented with stages I or II cancer and 73.8 per cent with stage III disease. The dominant histopathological type was infiltrating ductal cancer (49.2 per cent), followed by undifferentiated anaplastic carcinoma (33.3 per cent). Burkitt's lymphoma occurred in five patients and developed concurrently and rapidly during lactation in four. The prospective study did not demonstrate that age at menarche or first full-term pregnancy, duration of breast feeding or parity were risk factors in black women.


Managing swabs in the operating theatre: a new method. The swab count has traditionally used a swab rack. A new alternative 'bag' method involves placing used swabs in batches of five into plastic bags which are sealed and stored in a bin. A randomized prospective study was carried out to compare these two methods. Twenty consecutive ear, nose and throat cases were randomized to rack or bag collection. Swab-related activities were divided into three categories and analysed by formal time-and-motion criteria. Blood contamination of operating theatre and circulating personnel was recorded. The time involved in all three swab-related activities was significantly less using the bag technique. There was no theatre blood contamination using this method, but significant contamination occurred using the rack. Circulating theatre personnel were minimally contaminated in two cases using the bag method but were grossly contaminated in all ten cases using the rack method. The bag technique is therefore safe and time efficient.


Mechanism of action of injection therapy for bleeding peptic ulcer. The effects of intramucosal injection of 1:100,000 adrenaline, 5 per cent ethanolamine and normal saline were determined in experimentally created, acutely bleeding gastric mucosal wounds in rabbits. The mean(s.d.) bleeding rate was decreased from 2.3(0.4) to 0.2(0.02) ml/min by adrenaline (P < 0.01), but increased by 1 ml 5 per cent ethanolamine to 4.0(0.6) ml/min (P < 0.05). Normal saline had no haemostatic effect, suggesting that local tamponade is not important. In separate experiments endoscopic injections of 5 per cent ethanolamine, 1:100,000 adrenaline and normal saline were made in the gastric antrum of rabbits. After 48 h the degree of inflammation was greatest with ethanolamine but, despite tissue necrosis and venous thrombosis, neither endarteritis nor arterial thrombosis occurred. Injections of 5 per cent ethanolamine and 80 per cent ethanol placed next to the ear arteries of rabbits caused local ulceration and necrosis, but endarteritis and arterial thrombosis were again absent.


Selective necrosis in hamster pancreatic tumours using photodynamic therapy with phthalocyanine photosensitization. Photodynamic therapy (PDT) is often thought to be able to effect selective tumour necrosis. This therapeutic selectivity, based on transient differences in tumour: normal tissue photosensitizer concentration ratios, is rarely useful clinically in extracranial tumours, although PDT itself may be of value by virtue of the nature of the damage produced and healing of normal tissue by regeneration. This report describes the effects of PDT on normal pancreas and chemically induced pancreatic cancers in the hamster, where a different mechanism of selective necrosis may be seen. Photosensitizer distribution in normal and neoplastic pancreas was studied by chemical extraction and fluorescence microscopy. Correlation of distribution studies with necrosis produced by PDT shows that the photodynamic dose (product of tissue concentration of sensitizer and light dose) threshold for damage is seven times as high for normal pancreas as for pancreatic cancer. Tumour necrosis extended to the point where tumour was invading normal areas without damaging the normal tissue. In rat colonic cancer, photodynamic dose thresholds in tumour and normal tissue are similar and so such marked selectivity of necrosis is not possible. The reason for this selectivity in the pancreas is not clear, but recent evidence has suggested a difference in response to PDT between normal and neoplastic pancreatic cell lines and the presence of a singlet oxygen scavenger in normal pancreas is postulated. Furthermore, the present fluorescence microscopy studies suggest that tumour stroma contains the highest level of photosensitizer and thus receives the highest photodynamic dose during PDT. These results suggest a possible role for PDT in treating small pancreatic tumours or as an adjuvant to other techniques, such as surgery, that reduce the main bulk of tumours localized to the pancreas.


Duodenogastric reflux enhances growth and carcinogenesis in the rat pancreas. Surgery for peptic ulcer disease may increase the risk of pancreatic cancer. The effect of duodenogastric reflux on pancreatic carcinogenesis was tested, and changes in the circulating levels of cholecystokinin (CCK) and gastrin were measured. Male Wistar rats (n = 40) weighing 250-300 g were randomized to undergo gastrotomy (control) or split gastrojejunostomy (to produce complete duodenogastric reflux) and then to receive azaserine (30 mg/kg/week intraperitoneally) or saline injections for 3 weeks. At 6 months, blood CCK was assayed and the pancreas was excised for quantitative estimation of atypical acinar cell foci (AACF), the precursor lesions of carcinoma. Rats that had undergone split gastrojejunostomy weighed 15-19 per cent less than controls (P < 0.05), but their relative pancreatic weight (mg pancreas per 100 g body-weight) was 52-60 per cent greater (P < 0.001). Acidophilic AACF occurred only in azaserine-treated rats with duodenogastric reflux. Although plasma CCK concentrations were unchanged, split gastrojejunostomy increased basal and postprandial gastrin levels by 98-175 per cent (P < 0.05). Duodenogastric reflux produces sustained hypergastrinaemia and promotes experimental pancreatic carcinogenesis.


Renal tubular cell injury and serum phospholipase A2 activity in acute pancreatitis. Early diagnosis of threatening renal complication is essential for the adequate treatment of acute pancreatitis. Deposition of phospholipase A2 (PLA2) in rat renal proximal tubular cells has been observed in experimentally induced acute pancreatitis. The value of measuring the catalytic activity of PLA2 in serum as an early warning of developing renal tubular cell injury was therefore investigated in a prospective study of 31 consecutive patients suffering from acute pancreatitis. A positive correlation was found (r = 0.66, P < 0.001) between the highest serum PLA2 activity, as measured early in the course of acute pancreatitis, and the highest N-acetyl-beta-glucosaminidase (NAG):creatinine ratio in the urine. The correlation between the highest serum concentration of immunoreactive pancreatic PLA2 and the highest urinary NAG:creatinine ratio was weaker (r = 0.36, P < 0.05). These results indicate that the measurement of the catalytic activity of PLA2 in serum early in acute pancreatitis may provide a simple test for the detection of threatening renal complication.


Laparoscopic cholecystectomy as a routine procedure for gallstones: results of an 'all-comers' policy. A total of 165 consecutive patients with gallstones were considered for laparoscopic cholecystectomy. Three were excluded. The median age was 52 years and 76 per cent were women. Eighteen patients underwent urgent operation. Laparoscopic cholecystectomy was successful in 160 of the 162 patients (99 per cent). The two failures were the result of dense adhesions and stones in the bile duct. There were no deaths but major complications occurred in three patients: fenestration of the colon sutured laparoscopically; bleeding from a cannulation site and subsequent laparotomy for a strangulated hernia; and subphrenic abscess. There were 13 minor complications, but no bile duct injuries or peritonitis. The median postoperative hospital stay was 1 day. Bile duct stones were present in 14 patients (9 per cent) and were removed by endoscopic sphincterotomy (11 patients), by laparoscopic exploration of the common duct (two) and by conversion to laparotomy (one). These results suggest that laparoscopic cholecystectomy is applicable to the large majority of patients who require elective or urgent cholecystectomy, if appropriate radiological and endoscopic support is available.


Management of common bile duct stones using a second-generation extracorporeal shockwave lithotriptor. Fifty-four patients with common bile duct stones (8-36 mm in diameter) that could not be removed after endoscopic sphincterotomy, even with the use of mechanical lithotripsy, underwent extracorporeal shockwave lithotripsy (ESWL) using a Siemens Lithostar. Their median age was 75.5 (range 34-89) years. Patients received 4000-6000 shocks per session over approximately 60 min. Seventeen underwent two sessions and two patients three or more. Thirty-seven patients had one stone, ten had two, and seven had three or more. Spontaneous clearance of fragments occurred in only three patients before further endoscopic retrograde cholangiopancreatography was performed to remove fragments. Stones were removed and ducts cleared endoscopically in 35 patients, giving a total of 38 of 54 patients (70 per cent) with complete duct clearance. Fragmentation in response to lithotripsy was dependent on stone size; the number of stones had little effect. ESWL was well tolerated without any haematological or biochemical abnormality. Computed tomography in the first 20 patients showed no hepatic or pancreatic change after treatment. ESWL combined with endoscopic extraction of fragments is an alternative to surgery when preliminary endoscopic extraction and mechanical lithotripsy have failed.


Operative common bile duct imaging by operative cholangiography and flexible choledochoscopy. A consecutive series of 108 common bile duct (CBD) explorations was studied to examine the efficacy of routine operative cholangiography and flexible choledochoscopy in the identification of choledocholithiasis. CBD exploration was performed according to the findings of routine operative cholangiography. Nine negative explorations were performed, only one of which would have been avoided had selective cholangiography been employed. Eight patients had unsuspected choledocholithiasis that would have been missed if selective operative cholangiography had been used. Flexible choledochoscopy identified CBD stones on 97 occasions; no additional retained stones were found on subsequent T tube cholangiography. In two cases stones were seen but could not be removed; immediate identification allowed planning for early removal. Flexible choledochoscopy is the most effective method of CBD exploration and should be used in all patients with suspected choledocholithiasis.


Laparoscopic versus open appendicectomy: a prospective evaluation. A prospective evaluation of laparoscopic surgery for acute appendicitis over a 6-month period is reported. Sixty-five patients with signs and symptoms of appendicitis necessitating surgery were assigned to open (n = 36) or laparoscopic (n = 29) appendicectomy. Thirty-seven patients were female (22 open) and 28 were male (14 open). The median age was 24 (range 14-64) years for open appendicectomy and 18 (range 14-60) years for the laparoscopic procedure. The mean postoperative stay for open operation was 4.8 (range 1-21) days and for the laparoscopic route 2.2 (range 1-11) days (P < 0.05). Inflammation was confirmed histologically in 72 per cent of the open cases and in 74 per cent of the laparoscopic cases (P not significant). The wound infection rate was 11 per cent (n = 4) for open and 4 per cent (n = 1) for laparoscopic appendicectomy (P < 0.05). The median anaesthesia time was 52 (range 15-90) min for open appendicectomy and 48 (range 20-120) min for laparoscopic surgery (P not significant). After open appendicectomy patients had a median of 5 (range 2-12) intramuscular injections of analgesia compared with a median of 1 (range 0-5) in the laparoscopic group (P < 0.05). Two laparoscopic operations were converted to an open procedure. The results suggest that emergency laparoscopic appendicectomy should be explored further as an alternative to open surgery for acute appendicitis.


Role of sequential leucocyte counts and C-reactive protein measurements in acute appendicitis. The accurate clinical diagnosis of acute appendicitis is difficult, and many techniques have been suggested to improve diagnostic accuracy such as laparoscopy, ultrasonography and barium enema examination. In this study serial total leucocyte counts and serial C-reactive protein (CRP) concentrations in acute appendicitis were measured. The sensitivity and specificity of serial leucocyte counts in acute appendicitis were 92 and 100 per cent, and for CRP concentrations 69 and 75 per cent, respectively. The sensitivity and specificity of serial total leucocyte counts fulfilled the criteria for a diagnostic test. It is suggested that in patients with equivocal clinical findings, clinical observation combined with serial leucocyte counts may improve decision making.


Decreased sensitivity of muscarinic but not 5-hydroxytryptamine receptors of the internal anal sphincter in neurogenic faecal incontinence. Previous studies of the internal anal sphincter in patients with neurogenic faecal incontinence have indicated an abnormality of the adrenergic innervation, but little is known about the responsiveness of other receptors in the internal and sphincter in this condition. In this study the in vitro sensitivity to carbachol and 5-hydroxytryptamine (5-HT) of muscle strips from patients with neurogenic incontinence (n = 6 and n = 7) and from control patients (n = 9 and n = 10) was examined. Preparations of internal and sphincter from patients with incontinence were less sensitive to the relaxant actions of carbachol than preparations from the control group. The pD2 value for carbachol (i.e. the negative logarithm of the concentration for half-maximal response) was significantly greater in the controls than in the incontinent group (mean(s.e.m.) 6.03(0.15) versus 5.43(0.24), P < 0.05). There was no significant difference in the contractile responses to 5-HT, which had pD2 values of 6.93(0.13) and 6.63(0.27) for the control and incontinent groups respectively. The unaffected state of the 5-HT receptor and the subsensitivity of the muscarinic receptor are discussed in relation to intrinsic neural control of the internal and sphincter in neurogenic faecal incontinence.


Screening for colorectal carcinoma: an analysis of the sensitivity of haemoccult. The sensitivity of Haemoccult for asymptomatic colorectal carcinoma has been estimated in a large randomized controlled trial of mass population screening, with a minimum follow-up of 2 years. A total of 111 cancers were diagnosed in those who completed the screening tests; of these, 36 appear to have been missed by Haemoccult and 75 were detected by the test, giving an overall sensitivity of 67.6 per cent. Haemoccult was shown to be significantly more sensitive for carcinoma of the sigmoid and descending colon than for rectal or right-sided cancers (81 versus 45 and 47 per cent, respectively). The sensitivity was higher when tests were completed over 6 rather than 3 days (74 versus 65 per cent), but this difference was not statistically significant. There was no evidence for a detrimental effect on tumour stage of a false-negative Haemoccult test; indeed, a higher proportion of the interval cancers were Dukes' A tumours than cancers in the control group.


Local recurrence after anterior resection for rectal cancer using a double stapling technique. Fifty-five patients of mean age 69 (range 41-96) years with rectal cancer (Dukes' A:B:C, 11:24:20) underwent anterior resection using a double stapling technique under the care of one consultant surgeon between 1983 and 1988. The mean distance of the anastomosis from the anal margin was 7.2 (range 4-13) cm. The clinical leak rate was 9 per cent (five patients). There were three postoperative deaths from pulmonary embolism, lower limb ischaemia and renal failure. On prospective follow-up, 35 patients had no evidence of local or systemic cancer a median of 32 (range 24-84) months after operation; seven have died from unrelated diseases and ten from metastatic cancer. Pelvic recurrence, in four patients at 9, 11, 12 and 50 months, has occurred only in association with widespread metastasis. These results suggest that the theoretical risks of an increase in the local recurrence rate of rectal cancer after resection using a double stapling technique are not substantiated.


Timing and method of reversal of Hartmann's procedure. The outcome of 145 patients undergoing Hartmann's resection between 1973 and 1989 has been reviewed. The mortality rate of the primary procedure was 8 per cent. Eighty patients proceeded to reanastomosis. Multifactorial analysis of these patients was undertaken to determine the risk involved. The interval between the primary and secondary procedures was found to be the most important factor. Six of 12 patients had clinical evidence of a leak when this interval was < 3 months, compared with seven of 28 for 3-6 months, and none of 40 when the second operation was delayed for > 6 months. All deaths (three patients) and clinical septicaemia (four) occurred in the two 'early' groups. All colovaginal fistulae (three patients) and strictures (three) were associated with stapled anastomoses. No association was found between the complication rate following reanastomosis and the initial pathology or grade of surgeon undertaking the secondary operation.


Hippocampal volumetric and morphometric studies in frontal and temporal lobe epilepsy. The most common temporal lobe pathology is Ammons Horn sclerosis (AHS), and several different imaging techniques have been utilized to detect this with varying success. We describe the clinical application of magnetic resonance imaging (MRI) using a three-dimensional volume technique which allows total hippocampal volume to be measured and symmetry evaluated. Hippocampal surface area was calculated in sequential 1.5 mm thick contiguous images, using a GE IC workstation. Total volumes and surface areas were calculated. The cross-sectional surface area at 1.5 mm intervals was displayed graphically, permitting morphometric analysis of the hippocampus throughout its length. Focal atrophy within any part of the hippocampal formation (HF) and its extent could thus be assessed. Patients with well-lateralized temporal lobe epilepsy (TLE) (n = 20) and well-defined frontal lobe epilepsy (FLE) (n = 20) were studied, and volumes compared with normal values derived from 10 neurologically normal controls. Asymmetric hippocampal volume loss was demonstrated in all 20 patients with clinically typed TLE, but not in normal controls or patients with FLE. Volume loss distribution was anterior in 12 patients, posterior in one patient and widespread in seven patients. Secondarily generalized seizures were strongly associated with widespread loss. This method of surface area and volumetric analysis of the hippocampus in TLE can demonstrate asymmetry and focal involvement, and help distinguish between hippocampal and frontal pathologies.


Movement-related potentials recorded from supplementary motor area and primary motor area. Role of supplementary motor area in voluntary movements. Movement-related potentials (MRPs) were recorded from subdural electrodes chronically implanted in the interhemispheric fissure in two patients being evaluated for epilepsy surgery. Different types of movements (finger, foot, tongue and vocalization) were executed. Foot movements elicited a clearly defined, well-localized slow negativity or positivity (Bereitschaftspotential, BP) preceding electromyogram (EMG) onset. These BPs were seen from the contralateral primary motor foot area and also from bilateral supplementary motor areas (SMAs) with equivalent amplitudes and temporal evolutions. A steeper potential [negative slope (NS')] occurred about 300 ms before EMG onset and the motor potential (MP) started 100 ms before EMG onset. Negative slopes and MPs also arose from the contralateral primary motor area as well as from the bilateral SMAs. Finger movements elicited well-localized BPs and NS' which were generated from the bilateral SMAs, but were of higher amplitude on the contralateral SMA. Motor potentials started 50 ms prior to EMG onset and arose exclusively from the contralateral SMA. Tongue protrusions and vocalizations also elicited BP, NS' and MP which were seen in the bilateral SMAs. Movement-related potentials for different types of movements had a somatotopic distribution in the SMA, which was consistent with the SMA somatotopic organization defined by electrical simulation. Movement-related potentials for tongue movements and vocalization had a similar distribution and waveform. It was concluded that bilateral SMAs generate well-defined MRPs consistent with the assumption that the SMA plays a significant role in the organization of voluntary movements. However, the MRPs from the bilateral SMAs do not have characteristics which are different from those of the primary motor area. This suggests the hypothesis of 'supplementary' function for SMA, and does not support the hypothesis of 'supramotor' function.


Effects of focal transcranial magnetic stimulation on simple reaction time to acoustic, visual and somatosensory stimuli. In a simple reaction time (RT) paradigm, magnetic stimulation of different intensities was delivered over different scalp positions and at variable delays before (negative) or after (positive) the go-signal. Magnetic stimulation shortened RT to different go-signals (auditory, visual and somatosensory stimuli) by approximately 30 ms when delivered over the motor cortex contralateral to the responding arm at intensities below motor threshold. This effect was maximal at a delay of approximately +10 ms. A similar effect was found with suprathreshold stimulation to the ipsilateral motor cortex. Magnetic stimulation over other scalp areas did not affect RT regardless of the delay. No differences were found between the effects on elbow flexion and thumb abduction. The shortening of RT was not associated with changes in the timing development of premovement excitability increase in the motor cortex. We conclude that magnetic stimulation shortens RT by inducing an earlier initiation of this excitability increase.


Conceptual apraxia in Alzheimer's disease. Theoretical models of praxis have two major components, a praxis conceptual system that includes knowledge of tool use and mechanical knowledge and a praxis production system that includes the information needed to program skilled motor acts. Because patients with Alzheimer's disease may have an impairment of the central conceptual system, we wanted to learn if they had a conceptual apraxia by testing their knowledge of the type of actions associated with tool use, their ability to associate tools with objects that receive their action, their ability to understand the mechanical nature of problems and the mechanical advantages tools may afford. We studied 32 subjects with probable Alzheimer's disease and 32 controls by examining tool-action relationships and tool-object associations. We tested mechanical knowledge by having subjects select alternative tools and solve mechanical puzzles by developing new tools. The Alzheimer's group was subdivided into four groups based on the presence or absence of ideomotor apraxia and a lexical-semantic deficit. Results indicated that each of the four Alzheimer's groups differed from normal controls on at least some measures of conceptual apraxia, suggesting that Alzheimer's patients do have a disturbance of the praxis conceptual system and that impairment of this system is not directly related to language impairment or ideomotor apraxia.


Identifying the afferents involved in movement-induced pain alleviation in man. It has been clearly established that the perception of nociceptive stimulus decreases in intensity when movement is initiated in the part of the body to which the stimulus is applied. The pain alleviation is probably at least partly due to the activation of afferents which occurs during the movement. The present experiments were carried out with a view to investigating which groups of afferent fibres is mainly responsible for the gating of the nociceptive messages which occurs during movements. In eight volunteers we investigated the changes in the amplitude of the nociceptive leg flexion reflex (RIII) when the subjects were at rest, when they were performing active or passive ankle movements and when the spindle proprioceptive pathway was mobilized by applying vibratory stimulation to the Achilles tendon. Similar experiments were also carried out with eight other volunteers after anaesthetizing the ankle skin mechanoreceptors. This method was chosen because a clear-cut correlation is known to exist between the amplitude of the nociceptive motor reflex and the intensity of the pain perceived by the subject. The data obtained clearly show that anaesthesia of cutaneous mechanoreceptors connected to the large diameter afferent fibres prevented the decrease in the motor response which otherwise accompanied both active and passive movements. Activation of the Ia fibre group by tendon vibration resulted on the contrary in an increase in the amplitude of the motor response. Movement-induced pain alleviation therefore does not mainly involve the activation of the Ia group of fibres.


Texture discrimination in carpal tunnel syndrome. The ability to discriminate textured surfaces was measured in patients with carpal tunnel syndrome (CTS). Patients were initially diagnosed using clinical and electrophysiological criteria. The textured surfaces were gratings of alternating ridges and grooves. The gratings differed in their spatial period only, with the ratio of the ridge width to the groove width remaining constant (1:5). A two-alternative forced-choice paradigm was employed in which subjects, both patients and age-matched controls, rubbed their index finger (D2) or little finger (D5) back and forth across the surfaces. The grating spatial period at which subjects could discriminate a difference between the standard grating (spatial period = 2000 microns) and the comparison grating (spatial period in the range 2000-2900 microns) with a probability of 0.75 was taken as the measure of discriminative ability. Statistical comparison of the mean 75% values showed that: (i) when patients used D2 their discriminative ability was significantly impaired in comparison with the discriminative ability of controls using either D2 or D5; (ii) there was no significant difference in discriminative ability between patients and controls when patients used D5 to discriminate the textures; (iii) the 75% values for patients using D2 or D5 did not differ significantly. The degree of abnormality of each patient's sensory evoked potential did not allow us to predict their subsequent performance on the discrimination task.


Recurrent Guillain-Barré syndrome. Clinical and laboratory features. The clinical and laboratory features of recurrent Guillain-Barré syndrome (RGBS) were reviewed in 12 patients in whom a total of 32 episodes fulfilled accepted criteria for Guillain-Barré syndrome (GBS). All patients were asymptomatic or only mildly symptomatic between attacks. In a given patient, the time to reach peak deficit from the onset of symptoms, the functional grade at peak deficit and the duration of the intervals between episodes varied considerably and unpredictably from one episode to the next. Analysis of these parameters across the entire group revealed no significant change as the number of attacks increased. The distribution of weakness varied between episodes with the possible exception of features of the Miller Fisher variant which were more constant. Tremor was noted in two patients and enlarged nerves in one patient. There was no evident response to immunosuppressive therapy. Results of cerebrospinal fluid (CSF) analysis and nerve conduction studies during recurrences were those expected in typical monophasic GBS. On nerve biopsy, onion bulb formations were sometimes observed after several recurrences. The following characteristics of RGBS may be sufficiently distinctive from those of chronic relapsing polyneuropathy to justify their nosological separation: rapid onset of symptoms with subsequent complete or near complete recovery, high incidence of an antecedent illness, lack of an apparent response to immunosuppressive therapy and normal CSF protein levels at the onset of a recurrence.


Torsional nystagmus. A neuro-otological and MRI study of thirty-five cases. Thirty-five patients with torsional nystagmus (TN) underwent vestibular and ocular motor assessment and magnetic resonance image (MRI) scanning of the head. Patients were divided into two groups according to whether TN was predominant and present in primary gaze (Group I, 23 patients) or elicited by head positioning or gaze deviation and less prominent than other concurrent nystagmus (Group II, 12 patients). The main aetiologies in both groups were demyelination, vascular disease and posterior fossa tumours. In Group I, a frequent pattern of findings, occurring in 30-50% of cases, was a caloric canal paresis contralateral to the direction of the fast phases ('beat') of the TN, whereas the duration of horizontal caloric/rotational nystagmus and the slow-phase eye velocity of pursuit and of optokinetic nystagmus were all reduced in the direction of beating. The TN was more frequently and consistently modulated by vertical canal stimuli (head oscillation in roll) than by otolith stimuli (static tilt). Statistical analysis of the MRI showed significant overlap of abnormal MRI signals in the area of the vestibular nuclei, on the side opposite to the beat direction of TN. These results suggest that TN originates in a central imbalance of vertical semicircular canal function, resulting from lesions involving the vestibular nuclei on the opposite side of the TN. Group II was heterogeneous with no consistent pattern of neuro-otological findings, although lesions ipsilateral to the TN were frequent occurrence; in these cases cerebellar system lesions may have produced ipsilateral vestibular nuclei disinhibition.


Enduring dysmetria and impaired gain adaptivity of saccadic eye movements in Wallenberg's lateral medullary syndrome. Saccadic eye movements and the adaptive control of their amplitudes were examined in patients with Wallenberg's lateral medullary syndrome. Half of the patients had permanent saccadic dysmetria. Their primary saccades had asymmetric amplitudes: those made in response to an ipsilateral target step (i.e. to the lesion side) tended to be hypermetric and saccades made in response to a contralateral target step were strongly hypometric. Multiple correction saccades were needed for target fixation. The adjustment of the amplitude of artificially induced hypermetric saccades, called gain adaptivity, was examined experimentally by using double target steps. The first target step elicited the primary saccade which triggered a further target displacement. This second, intra-saccadic target displacement was opposite to the first target step and caused the primary saccade to overshoot the final target position. In this way a post-saccadic target position error was generated which had to be corrected for foveal fixation. With repetition of this stimulus sequence the saccadic control system of normal subjects made an adjustment in amplitude of the main saccade such that the overshooting gradually diminished. After a few hundred trials primary saccades became orthometric with respect to the final target position; in respect to the first target step they were, however, strongly hypometric. The experimental data show that patients with Wallenberg's syndrome had a reduced capability to readjust saccadic amplitude. This observation together with the enduring saccadic dysmetria suggest that adaptive gain control of saccades is impaired in patients with lesions restricted to the dorsolateral medulla. It is speculated that these lesions most likely disrupt olivo-cerebellar pathways which are believed to be of paramount importance in visuo-motor adaptation of the cerebellum.


Abnormalities of predictive saccades in hemi-Parkinson's disease. We studied reflexive and predictive saccades by direct current electro-oculography in nine patients with mild hemi-Parkinson's disease (hemi-PD) and in 16 age-matched controls. In five patients, the neurological syndrome was predominant on the right side of the body (RPD) and in four patients, on the left side (LPD). Reflexive saccades were elicited in response to the random appearance (timing and location) of a light-emitting diode (LED). Predictive saccades were elicited by alternatively illuminating LEDs at 10 degrees right and left, at various fixed frequencies (0.25-1 Hz). In the reflexive task, latency and amplitude of the saccades were normal in both PD groups. In the predictive task, mean saccade latency was not significantly different between patients and normals but there were two significant abnormalities in timing: first, but only in LPD, a directional asymmetry in latency (left greater than right, e.g. at 0.25 Hz, mean difference of 90 ms); secondly, especially in RPD, an abnormal tracking pattern, reflected by more variability of the mean value (for each group of patients) of saccade latency at each point in time, throughout a period of tracking at a given frequency. Predictive saccades were also strongly hypometric in both PD groups but especially in LPD (e.g. for rightwards saccades: controls = 19 degrees, SD = 1.6; LPD = 14 degrees, SD = 2.7; RPD = 15.7 degrees, SD = 2.3). These defects in saccadic timing and amplitude during predictive tracking were most salient at low frequencies. While these defects were largely bilateral, our findings suggest slightly different contributions of the right and left cerebral hemispheres to the spatial and timing components, respectively, that comprise optimal predictive saccadic behaviour.


Relationship between electromyographic activity and clinically assessed rigidity studied at the wrist joint in Parkinson's disease. The electromyographic (EMG) patterns recorded from wrist muscles during manually applied, repetitive flexion and extension movements of the wrist joint, used for simultaneous clinical assessment of rigidity, were studied in patients with Parkinson's disease and healthy subjects. Recordings were made whilst patients/subjects attempted voluntarily to relax the muscle of the arm whose wrist joint was manipulated. Individual patients were investigated before and at varying times after their routine daily medication as their clinical rigidity underwent associated modulations. It was often possible to induce additional alterations in clinical rigidity by instructing patients to perform an activation or Jendrassik-like manoeuvre (clenching the contralateral fist). In rigid patients, the approximately sinusoidal wrist displacements (60 deg, 1-1.5 Hz) typically elicited pronounced, cyclic modulations of EMG activities in wrist flexors and extensors; increases in EMG activity were phase-locked to the respective periods of muscle stretch. Stretch-related EMG activity reduced or disappeared as rigidity was abolished by drug therapy. The EMG patterns of patients showing cogwheel rigidity featured discrete, phasic bursts superimposed upon more generalized stretch-related increases in activity. In healthy subjects, showing no clinical rigidity, the pronounced cyclic modulations of EMG activity characteristic of rigid patients were absent during similar manually applied wrist displacements. Quantitative EMG measurements for individual patients, made 'on' and 'off' medication and as their rigidity fluctuated, indicated that mild (grade 1) and moderate (grade 2) rigidity was consistently associated with increased stretch-related activity compared with non-rigid conditions. Pair-wise statistical analysis indicated such increases in EMG to be significant. Similarly, the ratios of EMG activities in the stretched versus released muscles were significantly greater for grades 1 and 2 rigidity than in the absence of rigidity. Overall, the present findings support the view that enhancement of stretch reflex activity has a major role in the genesis of parkinsonian rigidity.


The auditory startle response in the Steele-Richardson-Olszewski syndrome and Parkinson's disease. The startle response to an unexpected auditory stimulus was studied in eight patients with a clinical diagnosis of the Steele-Richardson-Olszewski syndrome (SRO), 11 patients with idiopathic Parkinson's disease (PD) and 12 normal subjects. The patients with PD were studied 'on' at the time of maximal effect of their treatment; five of these patients were also studied in their 'off' state without treatment. The auditory startle response was absent in three patients with SRO: in the remaining five the latency to onset of earliest electromyography activity (EMG) of the auditory startle response was delayed and few muscles (orbicularis oculi, sternocleidomastoid and rectus abdominis) were recruited in the response. In PD the auditory startle response was similar to that recorded in normal subjects, both in terms of the pattern of muscles recruited and the amplitude of the EMG responses, but the latency of responses in orbicularis oculi and sternocleidomastoid muscles were significantly delayed. This result was not influenced by treatment with L-dopa. In patients with SRO the finding of an abnormal startle response is consistent with loss of neurons in the lower pontine reticular formation. This region is intimately involved in the startle response in animal studies. In patients with PD the late auditory startle response might be related to withdrawal of facilitatory input to brainstem centres and reticulospinal pathways from basal ganglia. The similarity of the responses in patients when 'on' and 'off' suggests these pathways are not under potent dopaminergic control.


Characterization of contralateral torques during static hip efforts in healthy subjects and subjects with hemiparesis. Contralateral torques exerted at the hip were measured in healthy subjects and subjects with hemiparesis performing unilateral static hip efforts in abduction, adduction, flexion and extension, in a sitting position, at two torque levels. In general, the ipsilateral hip efforts were accompanied by mirrored contralateral torques in both groups of subjects. The directionality of these contralateral torques indicates that their action at the pelvis is mechanically opposite to the ipsilateral efforts, suggesting that they ensure the stabilization of the pelvis. In healthy subjects, analyses of variance showed no difference in the magnitude of the contralateral torques with regard to which limb was used to perform the task. However, a significant increase in magnitude was demonstrated in the contralateral torques concurrent with the increasing level of effort requested ipsilaterally. In hemiparetic subjects, when performing the tasks with their paretic limb, the magnitude of the contralateral torques was significantly increased in the non-paretic limb when compared with those measured in the paretic limb during non-paretic limb efforts. Based on the present results, a model of postural control is presented to explain the relationship between the ipsilateral and contralateral torques. Using this model, it is hypothesized that the increased contralateral torques observed in hemiparetic subjects when performing the tasks with their paretic limb is related to the weakness of the paretic muscles. The clinical importance of exercises used for the re-education of the paretic lower limb in this population, which consist of resisting the non-paretic hip movements in order to strengthen the paretic hip muscles, is discussed in light of these results.


Dorsal horn and dorsal column dysfunction in intramedullary cervical cord tumours. A somatosensory evoked potential study. Median and tibial nerves somatosensory evoked potentials (SEPs) were recorded in 20 patients with intramedullary cervical spinal cord tumours. The longitudinal extent of the tumour was determined by magnetic resonance imaging (MRI) and the surgeon's intraoperative observations. Somatosensory evoked potentials to median or tibial nerve stimulation were abnormal in 85% of patients. Three groups were identified on the basis of the median nerve SEP findings: Group I (20% of cases) with normal SEPs responses; Group II (30% of cases) with impaired cervical dorsal horn postsynaptic activity (abnormal N13 potential) but preserved dorsal columns transmission up to the cortex (normal P14 and N20 potentials); Group III (50% of cases) where the dorsal horn activity and dorsal columns transmission were both impaired. The isolated abolition of the N13 potential observed in Group II reflects a functional dissociation between segmental dorsal horn and dorsal columns structures and should prompt myelographic investigations. Postoperative follow-up suggests that absent N13, P14 and N20 potentials before surgery carry an ominous functional prognosis. However, postoperative recovery of the N13 potential was found to occur in a few cases, suggesting that these tumours do not necessarily produce irreversible damage to the cervical dorsal horn neurons. Thus SEPs proved to have a high sensitivity in detecting cervical spinal cord dysfunction in intramedullary tumours, provided that a selective recording of the N13 potential is performed using a cervical-supraglottal derivation.


Viliuisk encephalomyelitis in the Iakut people of Siberia. Viliuisk encephalomyelitis (VE), a progressive neurological disorder with a fatal outcome usually in several months to 6 yrs after disease onset, is seen only among the Iakut people of Siberia. The acute meningoencephalitic phase of the disease is followed by progressive dementia, rigidity and spastic tetraparesis. The disease is characterized by multiple micronecrotic foci with marked inflammatory reactions and gliosis in the grey matter. The acute febrile onset, with cerebrospinal fluid (CSF) pleocytosis and increased protein in the CSF, the epidemiology and the inflammatory neuropathology suggest the disease is infectious. Studies on household spread indicate an incubation time of up to several years. Viliuisk encephalomyelitis was restricted to an ethically distinct group of Iakut people of the Middle Viliui region, but in recent decades, with migration from this region, it has been spreading into previously unaffected Iakut populations. The occurrence of multiple VE cases in households and introduction of the disease by migrants into new populations indicate horizontal transmission in a setting of long intimate contact.


Occurrence of a multiple sclerosis-like illness in women who have a Leber's hereditary optic neuropathy mitochondrial DNA mutation. Eight women are described who presented with bilateral, usually sequential, optic neuropathy, six of whom later developed a neurological syndrome indistinguishable from multiple sclerosis (MS). Magnetic resonance imaging, performed in five of the patients with an MS-like illness and in the two others with optic neuropathy alone, showed widespread white matter lesions as seen in MS. All of these women had matrilineal relatives with Leber's hereditary optic neuropathy, although this was not always apparent at presentation, and the most common mitochondrial DNA mutation associated with this disorder was detected in each of the women and their affected relatives. On the basis of observations made in these patients, the clinical features of Leber's hereditary optic neuropathy in males, and evidence for mitochondrially encoded peptides involved in the immune response in rodents, we propose that optic nerve damage in this disease could be immunologically mediated and that mitochondrial genes may contribute to susceptibility to MS.


Treatment of experimental NADH ubiquinone reductase deficiency with menadione. Chronic administration of diphenylene iodonium (DPI) to rats has been shown to model the characteristics of mitochondrial myopathy. Using this model the efficacy of menadione therapy has been assessed. Menadione treatment of rats injected with DPI was associated with improved weight gain and increased survival rate. This was accompanied by an improvement in muscle function as judged by analysis of isometric twitch tension of the gastrocnemius muscle (1 Hz for 20 min). The decline in phosphocreatine (PCr) levels in the gastrocnemius muscle during stimulation and delayed recovery in PCr after stimulation were similar in the menadione treated and untreated models. Menadione treatment of the DPI model resulted in a resting intramuscular pH significantly lower than control or untreated DPI rats, but a similar decline in intramuscular pH to the DPI rats during stimulation. The changes in metabolite levels were broadly similar in both the menadione treated and untreated DPI models following stimulation, although the changes, except for increased lactate concentration, were generally less marked in the menadione-treated DPI model.


Afferent and efferent connections of the bullfrog medial pallium. Horseradish peroxidase or tritiated proline was unilaterally injected into the medial pallium in bullfrogs in order to determine the sources of afferent projections to the medial pallium and the targets of pallial efferent projections. Some cells in all telencephalic centers, except the corpus striatum and the pars lateralis of the amygdala, project to the ipsilateral medial pallium. The medial pallium receives projections from fewer centers in the contralateral hemisphere, which include the medial septal nucleus, the pars medialis of the amygdala, the bed nucleus of the pallial commissure and the medial pallium. The raphe nucleus and the anterior thalamic nuclei appear to be the only sources of afferents to the medial pallium from outside the telencephalon. Efferents of the medial pallium are far more extensive than reported in earlier studies. The medial pallium projects ipsilaterally to all telencephalic nuclei, with the exception of a large part of the corpus striatum, and contralaterally to the medial septal nucleus, the olfactory tubercle, amygdala, medial pallium and bed nucleus of the pallial commissure. Extensive efferent projections also terminate in preoptic and hypothalamic regions, as well as in most thalamic relay nuclei, the pretectum and, possibly, the optic tectum. Similarities to the medial pallium in other tetrapods and to that in mammals suggest that the medial pallium in anurans is homologous to the subicular and CA fields and, possibly, the dentate gyrus in mammals. However, the extensive projections of the medial pallium to the dorsal thalamus and pretectum in anurans may be primitive features of the medial pallium retained in anurans, or uniquely derived features in anurans.


Sexual behavior and 2-deoxyglucose uptake in male red-sided garter snakes (Thamnophis sirtalis parietalis). The [14C]2-deoxyglucose (2-DG) technique was used to study patterns of neural activity associated with the species-typical courtship behavior of male red-sided garter snakes (Thamnophis sirtalis parietalis). Males in this species court females intensely during the first month following spring emergence from their prolonged winter hibernation. Autoradiographic methods were used to measure the accumulation of radioactive label in various regions through the brains of male garter snakes that courted females, males that failed to court females, and males not exposed to females. Male garter snakes that actively courted females showed a pronounced increase in 2-DG accumulation, and therefore presumably neural activity, in the region of the anterior hypothalamus/preoptic area, relative to males that did not actively court females. Males exposed to females (regardless of whether they courted or not) showed widespread, non-specific increases in 2-DG uptake relative to males not exposed to females. The results indicate the utility of the 2-DG technique for studying complex, species-typical behaviors in vertebrates.


The forebrain of the Pacific hagfish: a cladistic reconstruction of the ancestral craniate forebrain. The forebrain of the Pacific hagfish is described with regard to its morphology, cytoarchitecture, and secondary olfactory projections. The forebrain ventricular system is greatly reduced in adult hagfishes, although vestiges of ventricular structures can still be recognized. In order to clarify topographical relationships within the forebrain, we provide a three-dimensional reconstruction of the ventricular system, including the vestigial portions. Topography and embryology lead us to conclude that the 'primordium hippocampi' of previous authors is a diencephalic structure. For topographical and hodological reasons, we interpret the 'area basalis' of previous authors to be part of the preoptic region, and we identify a part of the so-called 'nucleus olfactorius anterior' as the homologue of the striatum. The laminated pallium is dominated by secondary olfactory projections and shows a high degree of regional cytoarchitectural specialization, as does the entire forebrain. In all, 42 cell groups are identified in the forebrain of hagfishes (compared to only about 25 in lampreys, for example). This surprisingly high degree of cytoarchitectural complexity prompted us to re-examine the phylogenetic history of craniate brains with this complexity in mind. In this paper we use cladistic methodology to reconstruct a morphotype, and we conclude that the forebrains of the earliest craniates may have been more complex than previously believed. This reconstruction includes hypotheses regarding the general morphology, secondary olfactory system, and visual system, as well as the relative sizes of major divisions of the forebrain in the earliest craniates.


Speech production, syntax comprehension, and cognitive deficits in Parkinson's disease. Speech samples were obtained that were analyzed for voice onset time (VOT) for 40 nondemented English speaking subjects, 20 with mild and 20 with moderate Parkinson's disease. Syntax comprehension and cognitive tests were administered to these subjects in the same test sessions. VOT disruptions for stop consonants in syllable initial position, similar to those noted for Broca's aphasia, occurred for nine subjects. Longer response times and errors in the comprehension of syntax as measured by the Rhode Island Test of Sentence Comprehension (RITLS) also occurred for these subjects. Anovas indicate that the VOT overlap subjects had significantly higher syntax error rates and longer response times on the RITLS than the VOT nonoverlap subjects--F(1, 70) = 12.38, p less than 0.0008; F(1, 70) = 7.70, p less than 0.007, respectively. The correlation between the number of VOT timing errors and the number of syntax errors was significant. (r = 0.6473, p less than 0.01). VOT overlap subjects also had significantly higher error rates in cognitive tasks involving abstraction and the ability to maintain a mental set. Prefrontal cortex, acting through subcortical basal ganglia pathways, is a component of the neural substrate that regulates human speech production, syntactic ability, and certain aspects of cognition. The deterioration of these subcortical pathways may explain similar phenomena in Broca's aphasia. Results are discussed in relation to "modular" theories.


Phonological error analysis, development and empirical evaluation. A method of error analysis, designed to examine phonological and nonphonological reading and spelling processes, was developed from preliminary studies and theoretical background, including a linguistic model and the relationships between articulatory features of phonemes. The usefulness of this method as an assessment tool for phonological ability was tested on a group of normal subjects. The results from the error analysis helped clarify similarities and differences in phonological performance among the subjects and helped delineate differences between phonological performance in spelling (oral and written) and reading within the group of subjects. These results support the usefulness of this method of error analysis in assessing phonological ability. Also, these results support the position that phonological approximation of responses is an important diagnostic feature and merely cataloging errors as phonologically accurate or inaccurate is inadequate for assessing phonological ability.


Auditory event related potentials during lexical categorization in the oddball paradigm. Event related potentials (ERPs) and reaction times (RTs) were recorded from 18 subjects, performing lexical categorization of words and nonwords. Three sets of monosyllable utterances, differentiated in semantic and rhyming attributes, were presented using the "oddball paradigm." ERPs included a sustained negativity which began approximately 100 msec after stimulus onset and peaked at approximately 400 mses (SN4) poststimulus, in response to target as well as to nontarget word stimuli. Semantic effects on SN4 latency were observed only for target utterances. Nonmeaningful word targets were associated with longer SN4 peak latencies as well as slower RTs compared to meaningful word targets. It is suggested that these longer latencies are due to a longer time required for an exhaustive search in permanent memory before categorizing a stimulus as a nonmeaningful word.


A computational account of deep dysphasia: evidence from a single case study. We present a case study of a patient, NC, who demonstrates the defining characteristics of deep dysphasia including semantic errors in repetition and an inability to repeat nonwords. In addition, NC's single word repetition and lexical decision performances are influenced by the imageability of the word input. NC also demonstrates a severely restricted phonological short-term memory (one digit, one word). Although his phonological discrimination is good in a minimal pairs judgment task, it becomes impaired when a delay is imposed or rehearsal is prevented between presentation of each member of a pair. NC's output is fluent but contains many formal paraphasias and neologisms. NC's total language profile is evaluated within the framework of Dell's (1986) interactive spreading activation model of language production. Adapting this output model to input processes, we account for all of NC's deep dysphasic symptoms as well as his pattern of production in a way that is more parsimonious than other attempts to model this disorder. In particular, we suggest that the semantic and formal paraphasias in naming and repetition result from a pathological increase in the rate of decay of primed nodes in the semantic-lexical-phonological network. This rapid decay increases the probability that phonologically and/or semantically related lexical nodes primed by top-down and bottom-up feedback during the operation of lexical activation and retrieval will be activated and selected instead of the lexical target. The advantages of using this model to account for aphasic symptoms and the implications for other lexical theories are discussed.


Lexical tones in Thai after unilateral brain damage. An acoustic perceptual investigation of the five lexical tones of Thai was conducted to evaluate the nature of tonal disruption in patients with unilateral lesions in the left and right hemisphere. Subjects (n = 48) included 10 young normal adults, 10 old normal adults, 11 right hemisphere nonaphasics, 9 left hemisphere fluent aphasics, and 8 left hemisphere nonfluent aphasics. The five Thai tones (mid, low, falling, high, rising) were produced in isolated monosyllables, presented for tonal identification judgments, and measured for fundamental frequency (Fo) and duration. Results of an analysis of variance indicated that left hemisphere nonfluent speakers signaled and tonal contrasts at a lower level of proficiency. The extent of their impairment varied depending on severity level of aphasia. When compared to normal speakers, tonal identification for less severe nonfluent aphasics differed more in degree than in kind, and for more severe nonfluent aphasics differed both in kind and in degree. Acoustic analysis revealed that with the exception of one left nonfluent, average Fo contours were comparable in shape across speaker groups. Variability in Fo production, however, was greater in left nonfluent speakers than in any of the other four groups of speakers. Issues are discussed regarding the extent and nature of tonal disruption in aphasia and hemispheric specialization for tone production.


Dysnomia in Alzheimer's disease: an evaluation of neurobehavioral subtypes. The relative influence of perceptual and semantic features on naming performance was investigated with reference to the neurobehavioral profiles displayed by patients with Alzheimer's disease (AD). Forty-one patients were classified as manifesting a verbal, visual, or global subtype based upon their pattern of neuropsychological functioning. Perceptual characteristics of to-be-named pictures were varied by manipulating the amount of line detail, whereas semantic qualities were varied by altering word frequency norms. All AD subtypes were less accurate than normal elderly controls in naming low frequency pictures. Patients and controls took longer to name low frequency and high complexity pictures, and this effect was comparable across the AD groups. Patients with predominantly visual deficits were significantly slower in naming than controls, and those with verbal impairments made a higher proportion of semantic naming errors when compared to patients displaying visual or severe global impairments. These results suggest that deficits in semantic processing contribute to naming dysfunction in AD, and they highlight the importance of examining dissociations among neurobehavioral subtypes.


The verbal transformation effect: auditory illusions as an index of lexical processing and homolog activation. A technique of inducing auditory illusions was used so that 192 undergraduates heard through headphones either three asynchronous dichotic versions of the same repeating word, at each of three auditory locations (left, center, and right), or only one single repeating word, monaurally or diotically, at each location. Independent illusory changes at each location were reported. Subjects' reports of lexical illusions, but not nonlexical illusions, were fewer at the right ear for three- vs. one-signal listening. These results support the homolog activation hypothesis (Boles, 1990) in which disruption of interhemispheric communication occurs for the hemisphere least capable of processing lexical information. In the current experiment homolog activation led to loss of lexical information when received from auditory positions other than the right, when three signals are presented. Lexical illusions (Verbal Transformations) may be the result of the misapplication of lexical knowledge in an ambiguous situation, listening to a recycling word without stabilizing syntactic or semantic context.


Slowed lexical access in nonfluent aphasia: a case study. A list priming paradigm (LPP) was used to examine the hypothesis that nonfluent aphasics are literally slowed down in automatic access to lexical information. In this paradigm, words are presented visually, and the subject's task is to make a lexical decision on each word as quickly as possible after its presentation. As soon as a lexical decision is made on one word, that word is removed and, after a predetermined interword interval, the next word is presented. In this way, a continuous "list" effect is obtained. Prior studies with both college-age and elderly subjects using the LPP have shown that, independently of age, on the LPP, priming obtains at interword delays of 500 to 800 msec, but not at either shorter or longer interword delays. In the study reported here, the LPP was used to examine delays at which priming obtained for LD, a nonfluent aphasic with a lesion primarily in the left frontal region. Examining interword delays ranging from 500 to 1800 msec, the subject showed priming only at a delay of 1500 msec, a considerably longer delay than that at which neurologically intact subjects have shown priming. Based on these results, it is argued that while automatic access is retained, that access is much slower in a nonfluent aphasic than in neurologically intact elderly subjects. These results are discussed in terms of how slowed lexical access might impact on discourse comprehension.


Stabilization of acetylcholine receptors at the neuromuscular synapse: the role of the nerve. The majority of acetylcholine receptors (AChRs) at innervated neuromuscular junctions (NMJs) are stable, with half-lives averaging about 11 days in rodent muscles. In addition to the stable AChRs, approximately 18% of AChRs at these innervated junctions are rapidly turned over (RTOs), with half lives of less than 24 h. We have postulated that RTOs may be precursors of stable AChRs, and that the motor nerve may influence their stabilization. This hypothesis was tested by: (i) labeling AChRs in mouse sternomastoid (SM) muscles with 125I-alpha-BuTx; (ii) denervating one SM muscle in each mouse, and (iii) following the fate of the labeled AChRs through a 5-day period when RTOs were either stabilized or degraded. The hypothesis predicts that denervation should preclude stabilization of RTOs, resulting in a deficit of stable AChRs in denervated muscles. The results showed a highly significant (P less than 0.002) deficit of stable AChRs in denervated as compared with innervated muscles. Control experiments excluded the possibility that this deficit could be attributed to independent accelerated degradation of either RTOs or pre-existing stable AChRs. The observed deficit was quantitatively consistent with the deficit predicted by a mathematical model based on interruption of stabilization following denervation. We conclude that: (i) the observed deficit after denervation of NMJs is due to failure of stabilization of pre-existing RTOs; (ii) RTOs at normally innervated NMJs are precursors of stable AChRs; (iii) stabilization occurs after the insertion of AChRs at NMJs, and (iv) motor nerves play a key role in stabilization of RTOs. The concept of receptor stabilization has important implications for understanding the biology of the neuromuscular junction and post-synaptic plasticity.


Osmotic stimulation differentially affects cellular levels of corticotropin-releasing hormone and neurotensin/neuromedin N mRNAs in the lateral hypothalamic area and central nucleus of the amygdala. To investigate the effects of osmotic stimulation on neural circuits concerned with non-neuroendocrine aspects of homeostatic regulation, the levels of the mRNAs coding for corticotropin-releasing hormone (CRH) and neurotensin/neuromedin N (NT/NMN) in the lateral hypothalamic area (LHA) and central nucleus of the amygdala (CEA) of animals given 2.5% saline to drink overnight were measured semiquantitatively using in situ hybridization. Overnight osmotic stimulation leads to converse effects on the levels of these two mRNAs in different anatomical regions; increased levels of both mRNAs are seen in the LHA, but levels decrease in the CEA. While a number of previous studies have shown that ppCRH mRNA in the paraventricular (PVH) and supraoptic (SO) nuclei of the hypothalamus may contribute to the neuroendocrine response to osmotic stimulation, the present results show that in response to osmotic stimulation neurons located outside the PVH and SO may also modulate their synthetic potential, not just for CRH but also NT/NMN. These results suggest that a physiological stimulus may modulate the levels of two peptides previously identified in circuits projecting from the forebrain to nuclei in the brainstem, and as such, CRH and NT/NMN may participate in the regulation by the forebrain of the autonomic and/or behavioral responses of the animal to dehydration. Furthermore, these data show that a particular stimulus has opposite effects on the level of both peptide mRNAs when expressed in two different cell groups, suggesting first, that these peptides may have more than one role in the response, and second, the existence and influence of differential control mechanisms.


Regional differences in the regulation of dopamine and noradrenaline release in medial frontal cortex, nucleus accumbens and caudate-putamen: a microdialysis study in the rat. Dopamine (DA) and noradrenaline (NA) extracellular levels have been measured by microdialysis in the medial frontal cortex (MFC), nucleus accumbens (NAc) and caudate-putamen (CP) under baseline conditions in awake and halothane-anaesthetized rats, and after application of three types of stimuli which are likely to activate the brainstem catecholaminergic systems: mild stressors (handling and tail pinch), rewarded behavior (eating palatable food without prior food deprivation) and electrical stimulation of the lateral habenular nucleus. Changes were studied with and without uptake blockade (10 microM nomifensine in the perfusion fluid). The influence of calcium concentration (1.2 or 2.3 mM in the perfusion fluid) on DA and NA overflow was tested in some cases. Handling and tail pinch stimulated both DA and NA overflow in MFC, and enhanced NA overflow in NAc. By contrast, these mildly stressful stimuli had only marginal effects on DA overflow in NAc and no effects on either DA or NA overflow in CP. Eating behavior was accompanied by increased DA and NA overflow in MFC but had no effect in NAc. These regional differences were similar also when the manipulations were applied under uptake blockade, which indicates that the more pronounced changes seen in MFC did not simply reflect a more sparse innervation (i.e. lower density of uptake sites) in the MFC compared to the more densely innervated NAc and CP areas. Stimulation of the lateral habenula induced a 2-3-fold increase in NA overflow in both MFC, NAc and CP but had no consistent effect on DA overflow in any region. The effect on NA release was abolished by a transection of the ipsilateral fasciculus retroflexus (which carries the efferent output of the lateral habenula). The results show that the forebrain DA and NA projections to cortical and striatal targets are differentially regulated during ongoing behavior, that the mesocortical and mesostriatal DA systems respond quite differently to stressful and rewarding stimuli; and that the NA projection to MFC (like the dopaminergic one) is more responsive to stressful and rewarding stimuli than the ones innervating the striatum (NAc and CP). The results support the view that environmental stimuli evoking emotional arousal (whether aversive or non-aversive) are accompanied by increased DA and NA release above all in the MFC and only to a minor extent in limbic and striatal areas.


Sex differences in the binding of type I and type II corticosteroid receptors in rat hippocampus. Binding parameters of soluble Type I and Type II receptors were assessed in hippocampus of adult, adrenalectomized, male and female rats. No sex differences in the number of either Type I or Type II receptors could be demonstrated between gonadally intact animals. When females treated with 17 beta-estradiol benzoate (10 micrograms/day) were compared with males, a statistically significant reduction in Type II receptors was observed in the females; progesterone produced no further decrease in receptor numbers. The amount of tissue-associated corticosteroid-binding globulin in gonadally intact animals (perfused with dextran-saline) was twice as great in females as males. Sex-dependent differences in these gonadally intact rats were found in the affinity, measured as the dissociation constant (Kd), of both the Type I and Type II receptors. For both receptors, affinity in cytosols from females was reduced. The difference for the Type II receptor was slight, but the Kd value of the Type I receptor was several-fold higher in females. The difference in affinity was evident with both natural and synthetic steroid ligands. There appears to be little, if any, difference in affinity between the hippocampal Type I and the Type II receptors in females. This suggests that the occupancy of Type I receptors in females is substantially less than that of males at low circulating concentrations of corticosteroids.


SDN-MPOA volume in male rats is decreased by prenatal stress, but is not related to ejaculatory behavior. A computer-assisted image analysis technique was used to measure the adult volume of the sexually dimorphic nucleus of the medial preoptic area (SDN-MPOA) in prenatally stressed male rats and in groups of non-stressed males and females. The SDN-MPOA of male offspring from dams stressed daily (i.e. three 45-min exposures to physical restraint and bright light) during the last week of pregnancy was significantly smaller than in males not exposed to stress, but was larger than in females. Maternal stress has been shown to attenuate the surge in fetal plasma testosterone (T) which normally occurs on days 18 and 19 of gestation in male rats. The present results suggest that suppression of T during prenatal development leads to an incomplete masculinization of the SDN-MPOA in male rats. There was no difference in SDN-MPOA volume between males that exhibited the ejaculatory pattern when tested with estrous females and males that failed to ejaculate in either the control or prenatal stress group. SDN-MPOA volume does not appear to be predictive of masculine ejaculatory performance.


Discharge response of cerebellar Purkinje cells to stimulation of C-fiber in cat saphenous nerve. Experiments were performed in cats under chloralose anaesthesia and immobilized by Flaxedil. The discharge responses of cerebellar Purkinje cells (PC) were recorded with a microelectrode. The spontaneous activities of PC consisted of simple spike (SS) and complex spike (CS). When the saphenous nerve was stimulated at a low intensity, which elicited the A-fiber input only, the discharge responses (A-CED) consisted of an early component with short latency and late component with long latency in PC-SS and PC-CS. After A-fibers were blocked selectively by the polarizing current, the stimulation at the strength of C-fiber suprathreshold evoked the characteristic responses (C-CED) of PC-SS and PC-CS with middle latency. However, the C-CED could not be evoked by the inputs of A- and C-fibers simultaneously. These results suggested that the pure C-fiber input reaching the cerebellar PC passed through not only climbing fibers, but also mossy fibers, and elicited the characteristic responses (C-CED); these responses were neither the early component nor late component of the A-CED. When A- and C-fiber were activated at the same time, the C-CED might be inhibited by the A-fiber inputs.


Cerebellar neurons and glia respond differentially to endothelins and sarafotoxin S6b. Endothelins (ETs) and sarafotoxin-S6b belong to a family of extremely potent vasoconstrictors which may also have a role as neuropeptides or neuromodulators in the central nervous system (CNS). We show, using single cell dynamic video imaging of intracellular free calcium ions ([Ca2+]i), that binding of ET to its receptors modulates [Ca2+]i of neurons as well as glial cells in primary cultures of rat cerebellum. At least two receptor subtypes, differing in both their ligand specificity and distribution, appear to be involved in the action of ETs and sarafotoxin S6b on these cells. One of these receptors may be a previously undescribed neuronal form of ET receptor. This is the first demonstration of a direct effect of ETs on neurons as well as glia in the CNS. These data support a possible role for ET as a neurotransmitter or neuromodulator in the CNS.


Stimulation in the ventral posterior lateral nucleus of the primate thalamus leads to release of serotonin in the lumbar spinal cord. Stimulation in the ventrobasal complex of the thalamus relieves neuropathic pain and inhibits spinal cord transmission of nociceptive information. Electrical stimulation of the ventral posterior nucleus of the thalamus elicited increases in extracellular serotonin concentration in the spinal cords of anesthetized monkeys. These results suggest that thalamic stimulation activates the raphe-spinal tract and thus implicates serotonin as a mediator of thalamic stimulation induced analgesia.


Inhibition of peptide release from invertebrate neurons by the protein kinase inhibitor H-7. The protein kinase inhibitor H-7 has been shown to prevent the potentiation of action potentials that normally accompanies an afterdischarge in the bag cell neurons of Aplysia. We have now shown that H-7 attenuates the release of ELH from these neurons during an afterdischarge without influencing the firing frequency or length of the afterdischarge.


The effect of axon injury on microtubule-associated protein MAP2 mRNA in the hypoglossal nucleus of the adult rat. High molecular weight microtubule-associated protein 2 (HW MAP2) is heavily concentrated in mature dendrites and may be critical for dendritic stability. Motor axon injury results in retraction of the dendritic tree which is associated with a decrease in MAP 2-like immunoreactivity (-LIR). Here we have shown with in situ hybridization that motor axon injury results in reduced expression of HW MAP2 mRNA in affected neurons. We conclude that axotomy induces a down-regulation of HW MAP2 synthesis.


Anisomycin and cycloheximide protect cerebellar neurons in culture from anoxia. Protein synthesis inhibitors have recently been shown to protect from ischemia-induced neuronal death in the rat hippocampus in vivo. In an attempt to further investigate the mechanism of neuronal death resulting from anoxia, cerebellar neurons grown in culture were exposed to an anoxic atmosphere in the presence of protein synthesis inhibitors. Anisomycin and cycloheximide (100 micrograms/ml) offered, respectively, a 97 +/- 4% and 26 +/- 13% protection against anoxia-induced neuronal death.


Electrophysiological evidence for reciprocal connectivity between the nucleus accumbens septi and ventral pallidal region. Responses of nucleus accumbens (NAS) neurons to ventral pallidum (VP) stimulation were examined in anesthetized rats. Results demonstrated: (1) NAS to VP projection neurons reside primarily in the relatively lateral aspects of the NAS, and (2) substantial VP to NAS feedback also exists. These feedback projections are widely distributed throughout the NAS. Moreover, functionally identifiable NAS neuronal subpopulations were revealed by analysis of unit responses to concurrent VP and fimbria stimulation: (1) most, but not all NAS units responded to VP and fimbria stimulation in qualitatively divergent ways; (2) many NAS units demonstrated monosynaptic convergence of fimbria and VP terminations onto individual NAS units; and (3) in other cases, identified NAS-VP projection neurons were also monosynaptically activated by fimbria stimulation.


The uptake of anionic and cationic amino acids by the isolated perfused sheep choroid plexus. The carrier-mediated uptake of anionic and cationic amino acids by the basolateral face (blood side) of the isolated perfused sheep choroid plexus was demonstrated using the paired-tracer dilution technique. The uptake of these two classes of amino acid was higher than at the blood-brain barrier with no cross-competition between them. In addition the uptake was markedly stereospecific with a high degree of selectivity and no interaction with the L-system amino acids.


Characteristics of caudal ventrolateral medullary neurons antidromically activated from rostral ventrolateral medulla in the rabbit. We made extracellular recordings from 107 spontaneously active neurons in the caudal ventrolateral medulla, after identifying the cells by antidromically activating them from the rostral ventrolateral medulla, in urethane-anesthetized rabbits. We tested the response of these neurons to inputs from baroreceptors and chemoreceptors. The median conduction velocity for antidromically activated neurons was 0.84 m/s. Raising blood pressure with intravenous noradrenaline excited 22% of 96 neurons tested, inhibited 61%, and had no effect on the remaining 17%. The spontaneous discharge rate of neurons excited by an increase in blood pressure was 1.6 +/- 0.3 spikes/s, lower than the discharge rate of neurons inhibited by this procedure (4.9 +/- 0.5 spikes/s). Excitation of chemoreceptors by hypoxia increased the discharge rate of 14/16 neurons tested in the group excited by baroreceptor inputs. In the group inhibited by baroreceptor inputs 21/35 neurons tested were excited and 12/35 neurons were inhibited by chemoreceptor inputs. Neurons excited by an increase in blood pressure were located in the previously defined caudal vasodepressor region and in a region just rostral to the obex, intermediate between the vasodepressor region and the rostral sympathoexcitatory region. These neurons may form part of the central inhibitory link in the baroreceptor-vasomotor pathway. Other antidromically activated neurons in the vasodepressor region may be inhibitory vasomotor cells with a function relatively independent of baroreceptor inputs, or they may be A1 catecholamine neurons, with axons passing through the rostral medulla en route to the forebrain.


Effects of central serotonin on autonomic control of heart rate in intact and baroreceptor deficient rats. The intracerebroventricular (i.c.v.) injection of serotonin (5-HT) increases blood pressure and decreases heart rate (HR) in conscious rats by activation of 5-HT2/1C receptors. Since the bradycardia is eliminated by pretreatment with a ganglionic or V1-vasopressin antagonist, we proposed that the decrease in HR results from an effect on cardiac autonomic activity which is potentiated by vasopressin. The present study aimed first, to further characterize mechanisms by which the i.c.v. injection of 5-HT (2.5 micrograms) decreases HR in conscious rats, and second to determine the cardiovascular responses to 5-HT (2.5 micrograms, i.c.v.) in rats with chronic sinoaortic deafferentation (SAD). In intact rats, the bradycardia elicited by 5-HT was eliminated by a combination of the muscarinic antagonist atropine and the beta-adrenoceptor antagonist sotalol; neither antagonist was effective alone. In rats with SAD, 5-HT produced a larger increase in blood pressure and a marked tachycardia, both of which were eliminated by the 5-HT2/1C antagonist LY 53857. Furthermore, in rats with SAD the 5-HT-induced increase in HR was blocked by sotalol alone. In conclusion, 5-HT (2.5 micrograms, i.c.v.) acts on central 5-HT2/1C receptors to increase arterial pressure. In intact rats this decreases HR by vasopressin-potentiated activation of baroreceptor reflexes and subsequent increase in vagal tone and decrease in cardiac sympathetic tone. In the absence of baroreflexes, a direct central effect of 5-HT to produce a beta-adrenoceptor-mediated cardioacceleration is unmasked.


Development of long-term subsensitivity to GABA in dorsal raphe neurons of amygdala-kindled rats. Previously we reported a long-term change in neuronal sensitivity to GABA following amygdala kindling. Dorsal raphe neurons of amygdala-kindled rats exhibited significant subsensitivity to GABA 4 weeks after the last fully generalized (Stage 5) seizure. We hypothesized that this alteration in GABA sensitivity might reflect neuronal changes corresponding to kindled seizure susceptibility and subsequent experiments have investigated this hypothesis. The progression towards neuronal subsensitivity to GABA during amygdala kindling can be correlated with the Stage to which an animal has been kindled. That is, when measured 4 weeks after the last kindled seizure, dorsal raphe neurons are supersensitive to GABA following a Stage 2 seizure, not different from controls following a Stage 3 seizure and subsensitive to GABA following a Stage 5 seizure. In addition, subsensitivity to GABA appears to be permanent in that it is still measurable 3 months after the last Stage 5 seizure. Thus, amygdala kindling produces long-term, perhaps permanent, changes in neuronal sensitivity to GABA and these changes reflect the Stage to which an animal has been kindled.


Role of endogenous opioid peptides in the acute adaptation to hypoxia. A non-lethal, hypoxic conditioning stimulus has been shown by Rising and D'Alecy to increase hypoxic survival time in mice. To determine if endogenous opioids alter the hypoxic conditioning-induced increase in hypoxic survival time, we administered naloxone (0.1, 1.0 mg/kg i.p.) or saline (0.3 ml i.p.) 5 min prior to conditioning. Sixty percent of the mice received the hypoxic conditioning stimulus consisting of three sequential hypoxic exposures (4.5% oxygen balance nitrogen for 1.5, 2 and 2.5 min) separated by 5 min of room air. The remaining mice did not receive hypoxic conditioning but instead remained in room air for this time. All mice were tested for hypoxic survival by first exposing them to 20 s of 8.5% oxygen balance nitrogen followed by exposure to 4.5% oxygen balance nitrogen. The hypoxic survival time was recorded as the time from the onset of the 4.5% oxygen to the cessation of spontaneous ventilation. Naloxone (1 mg/kg) completely blocked the adaptation to hypoxia induced by hypoxic conditioning (P = 0.003). Morphine (1, 5, 10 and 20 mg/kg) had no effect on hypoxic adaptation; however, 50 mg/kg morphine decreased the adaptation induced by conditioning (P less than 0.0001) possibly due to high dose toxicity. These data suggest that endogenous opioids are involved in the protective adaptation to hypoxia induced by prior exposure to non-lethal hypoxia.


Different effects of intracellular and extracellular TEA on voltage-dependent K currents of acutely isolated hippocampal CA1 neurons. Tetraethylammonium (TEA) effects on K currents were examined on either side of the membrane of hippocampal CA1 neurons by means of whole-cell voltage-clamp recording and intracellular perfusion. Recording media contained ion channel blockers to allow the selective activation of voltage-dependent K currents which consisted of a rapidly decaying component (A-current) and a delayed component. Voltage protocols were applied to separate the A-current from the delayed component. Results show that 10 mM extracellular TEA suppressed 50 +/- 11% (S.D., n = 4) of the delayed current at different levels of depolarization but had little effect on the A-current. In contrast 10 mM TEA applied by intracellular perfusion suppressed the A-current by 42 +/- 10% (S.D., n = 4) in addition to inhibiting the delayed currently 55 +/- 15% (S.D., n = 4). Both the intracellular and extracellular actions of TEA on K currents showed no voltage- nor time-dependency. The results suggest that voltage-dependent transient current (A-current) is mediated through a separate group of ionic channels distinct from those that sustained the delayed current. Furthermore, the asymmetrical effects of intracellular and extracellular TEA on the transient current are similar to those described for the A-current in molluscan neurons. This observation supports the notion that the structure of the ion channel mediating the A-current is closely conserved across different species.


Projections of anterior hypothalamic neurones to the dorsal and ventral periaqueductal grey in the rat. Projections of neurones in the rostral hypothalamus to the periaqueductal grey matter (PAG) of the rat were investigated using retrograde tracing of red and green fluorescent latex microspheres. Microspheres were injected into one of 4 PAG sub-divisions, namely the dorsal, dorsolateral, ventral and ventrolateral parts. The patterns of retrogradely labelled neurones in the hypothalamus from each of the 4 PAG sub-divisions were found to differ and these are described. The precise nature of projections of neurones in the anterior hypothalamic area (AHA) was investigated and it was found that neurones within a circumscribed area of AHA, the lateral area of the anterior hypothalamus (LAAH), projected predominantly to the dorsolateral PAG while neurones in immediately adjacent areas projected to either dorsolateral or ventrolateral aspects of the PAG. Double retrograde tracing studies, where the two different colour beads were injected into different subdivisions of the PAG, gave rise to very few double labelled hypothalamic neurones, indicating that neurones in the hypothalamus project to only one sub-division of the PAG. The functional significance of these pathways is discussed in relation to mechanisms of autonomic and sensory control.


Feedback control of limb stiffness and scaled phase invariance properties of skilled high-speed arm flexion movements of a loaded manipulator. In this and a previous experiment it has been observed that subjects produce innervation patterns (EMG) that are load specific, i.e., they produce concentration patterns for movements made with inertial loads and triphasic patterns for movements made with elastic loads. The protocol of these experiments prevented any adaptive responses to the load changes, therefore, it was assumed that pattern matching to load type was a real time updating response of the peripheral feedback systems. This updating response was assumed to be a mechanism for fine tuning the muscle torque by regulation of the mechanical impedance (stiffness) of the limb. Using a standard equation of motion, it was shown that the velocity is equal to the ratio of the muscle torque to the mechanical impedance. Substitution of this ratio for the ordinate of the scaled phase diagrams was then suggested as a real time updating mechanism to account for the scaled phase invariance recorded in this experiment and in the experiment reported by Ruitenbeek, J.C., Biol. Cybernetics 51 (1984) 11-20.


A novel m2-selective muscarinic antagonist: binding characteristics and autoradiographic distribution in rat brain. Although several m2-selective muscarinic antagonists have been described, they are not particularly potent. Thus, the development of potent m2-selective compounds remains an important goal. We now report that a bio-isoster of AQ-RA 741 is both one order of magnitude more potent and slightly more selective than previously described compounds. DIBA, a di-benzo derivative of AQ-RA 741, in which the pyridine of the tricycle is replaced with a benzene ring, had Ki values of 4, 0.3, 11 and 2 nM at m1 through m4 receptors, respectively. These values were determined in competition studies with [3H]N-methylscopolamine ([3H]NMS) in membranes from transfected A9 L cells (m1 and m3), rat heart (m2) and NG108-15 cells (m4). AQ-RA 741 had Ki values of 34, 4, 86 and 15 nM at each of these receptors. The autoradiographic distribution of DIBA binding sites was determined by competition studies of [3H]NMS in rat brain. At low concentration, DIBA reduced [3H]NMS binding most significantly from superior colliculi, thalamus, hypothalamus, pontine nucleus, and interpeduncular nucleus, and not appreciably from caudate nucleus, cerebral cortical regions, or hippocampus, consistent with its binding to m2 receptors. These data indicate that DIBA is the most potent, m2-selective muscarinic antagonist yet described. DIBA should therefore become a useful probe in future studies of muscarinic function.


Enhanced renal response to intracerebroventricular angiotensins II and III in spontaneously hypertensive rats. The acute effects of intracerebroventricular (i.c.v.) administration of angiotensin III (ANG III) on blood pressure (BP) and renal function were investigated in spontaneously hypertensive rats (SHR, n = 31) and Wistar-Kyoto (WKY) normotensive rats (n = 6). ANG II was also administered to the same rats for comparison of its renal effect. BP and renal clearance responses were measured before and during ANG injections. The results showed that i.c.v. injections of 1, 5 and 50 pmol of ANG III did not significantly alter BP in SHR, but a high dose of ANG III (50 pmol) caused a vasopressor effect (7 +/- 4 mmHg) in WKY rats. There were significant increases in renal plasma flow (RPF), glomerular filtration rate (GFR), urine flow, absolute and fractional excretions of sodium and potassium, osmolar clearance and free water reabsorption rate following i.c.v. administration of ANG III in both SHR and WKY rats. However, the enhancement in renal responsiveness to ANG III was greater in SHR than in the WKY group. At 5 pmol of ANG III, the peak increases in GFR (96 +/- 23%), diuresis (316 +/- 102%) and natriuresis (712 +/- 281%) in SHR were significantly greater than those in WKY rats (40 +/- 13%, 152 +/- 89%, 229 +/- 130%, resp.). The renal effect of central ANG III was blocked by i.c.v. ANG III antagonist, [Ile7]-ANG III, but was enhanced by bestatin, an ANG III metabolic enzyme inhibitor. I.c.v. administration of ANG II at 50 pmol increased BP in both SHR and WKY rats (14 +/- 3 and 10 +/- 3 mmHg, resp.). Greater diuretic and natriuretic responses to ANG II were also noted in SHR than in WKY rats. These results indicate that central ANG III is as active as ANG II in modulating renal function. Furthermore, the enhanced renal response to i.c.v. ANGs II and III in SHR suggests a hyperactive central RAS implicated in BP and body fluid regulation in this genetic hypertensive strain.


Exposure to DDT during a defined period in neonatal life induces permanent changes in brain muscarinic receptors and behaviour in adult mice. DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] is a potent neurotoxicant in both vertebrate and invertebrate species. We have previously reported that neonatal exposure to DDT affects the muscarinic cholinergic receptors (MAChR) in the cerebral cortex in the neonatal mouse, leading to permanent disturbances in the cholinergic system and behaviour of the animals as adults. In order to determine if there is a critical period for these effects, mice at the ages of 3-days, 10-days and 19-days were given a single low oral dose of DDT (0.5 mg/kg b.wt.). At adult age (4 months) the mice were tested for spontaneous behaviour: 'locomotion', 'rearing' and 'total activity', and were subsequently sacrificed for measurement of the density of MAChR and subpopulations of MAChR in the cerebral cortex by using the muscarinic antagonist quinuclidinyl benzilate, [3H]QNB, and agonist carbachol, respectively. A significant increase in spontaneous motor behaviour and a significant decrease in MAChR density in the cerebral cortex was only observed in adult mice receiving DDT at the age of 10 days. The induction of these disturbances is limited to peaks in the development of spontaneous behavioural activity and MAChR in the neonatal rodent.


Autoradiographic study of striatal D1 and D2 dopamine receptors in 6-OHDA-lesioned rats receiving foetal ventral mesencephalic grafts and chronic treatment with L-dopa and carbidopa. Foetal dopamine cell suspensions or sham preparations were implanted into the denervated striatum of rats with a unilateral 6-hydroxy-dopamine (6-OHDA) lesion of the medial forebrain bundle. Some animals were also treated with L-DOPA (200 mg/kg/24 h) and carbidopa (25 mg/kg/24 h) in the drinking water for 5 weeks, followed by a 3-week drug-free period. Rotational responses to apomorphine and (+)-amphetamine were assessed, and the density of D1 and D2 dopamine receptors was evaluated autoradiographically in striatal slices exposed to [3H]SCH 23390 or [3H]spiperone. Foetal grafts reduces apomorphine-induced contralateral rotation and prevented the development of apomorphine-induced stereotypy. Foetal grafts abolished (+)-amphetamine-induced ipsilateral rotation. These effects of the grafts were not altered by treatment with L-DOPA. A unilateral 6-OHDA lesion of the nigrostriatal pathway resulted in an ipsilateral increase in D2 receptor density most marked in the lateral and dorsomedial quadrants of the striatum compared with the contralateral side. Foetal ventral mesencephalic grafts implanted into the lesioned striatum decreased D2 receptor density to levels found in the contralateral intact striatum. Chronic L-DOPA and carbidopa treatment did not alter the effect of the grafts. A 6-OHDA lesion resulted in a reduction of D1 receptor density in the lateral areas of the lesioned striatum at Level 2. The presence of a foetal ventral mesencephalic graft either alone or together with L-DOPA treatment did not alter the lesion-induced changes in D1 binding density.


Central location of the motoneurons that supply the cucullaris (trapezius) of the clearnose skate, Raja eglanteria. A complex of three muscles (one lateral, one intermediate and one medial in position) in the clearnose skate, Raja eglanteria, is believed to be wholly, or in part, homologous to the cucullaris (trapezius). The retrograde transport of horseradish peroxidase was used to discover the central location of the motoneurons that supply each of these muscles. Motoneurons that project to the lateral muscle occupy the caudal part of the ventral nucleus of X. This nucleus is situated ventrolateral to the dorsal vagal motor column at caudal medullary levels, and lateral to the main ventral motor column of the rostral spinal cord. The axons of these motoneurons exit the medulla within the caudal vagal rootlets and course peripherally within the intestinal (visceral) ramus of the vagus nerve. Motoneurons that innervate the intermediate and medial muscles are located along the ventral border of the ventral column of gray at spinal cord segments 10-15. Their axons course peripherally within the ventral roots of spinal nerves. The caudal ventral nucleus of X, the nerve that supplies the lateral muscle, and the lateral muscle are likely homologues of the accessory nucleus, accessory nerve, and cucullaris (trapezius), respectively, among other fishes and tetrapods. Intermediate and medial muscles, based on the central location of motoneurons that supply them, are part of the longitudinal epaxial musculature and are not part of a trapezius complex.


Overlap of somatic and visual response areas in the Wulst of pigeon. The somatic and visual response areas of the Wulst were investigated electrophysiologically in pigeons. Somatosensory neurons are distributed in the hyperstriatum accessorium (HA), the hyperstriatum intercalatus superior (HIS) and the hyperstraitum dorsal (HD), mainly in HA. The radial nerve response area is relatively larger and overlaps the sciatic nerve area. Visual neurons are located in HA, especially the more superficial part of HA. In the Wulst, the somatic response area overlaps the visual area and there is somatosensory-visual convergence.


Distribution of hypothalamic, medullary and lamina terminalis neurons expressing Fos after hemorrhage in conscious rats. The immunohistochemical detection of the protein, Fos, has been used as an anatomical marker of activated neurons. Three conscious rats were hemorrhaged (4 ml, 20-25% of blood volume) and the distribution of Fos-stained neurons was compared to that in 4 rats which did not have blood removed. In hemorrhaged rats, a higher concentration of Fos-stained neurons was present in the lamina terminalis, particularly the subfornical organ and organum vasculosum of the lamina terminalis, and in the supraoptic and paraventricular nuclei of the hypothalamus. In the medulla, Fos-stained neurons were restricted to the nucleus of the tractus solitarius, area postrema and the ventrolateral medulla. We hypothesize that those neurons are involved in mediating the physiological responses to hemorrhage.