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Generation of spontaneous rhythmic activity is a distinct feature of developing spinal networks. We report that rat embryo organotypic spinal cultures contain the basic circuits responsible for pattern generation. In this preparation rhythmic activity can be recorded from ventral interneurons and is developmentally regulated. When chronically grown in the presence of an AMPA/kainate receptor blocker, this circuit expresses long-term plasticity consisting largely of increased frequency of fast synaptic activity and reduction in slow GABAergic events. We examined whether, once this form of homeostatic plasticity is established, the network could still exhibit rhythmicity with properties similar to controls. Control or chronically treated ventral interneurons spontaneously generated (with similar probability) irregular, network-driven bursts over a background of ongoing synaptic activity. In control cultures increasing network excitability by strychnine plus bicuculline, or by raising [K(+)](o), induced rapid-onset, regular rhythmic bursts. In treated cultures the same pharmacological block of Cl(-)-mediated transmission or high-K(+) application also induced regular patterned activity, although significantly faster and, in the case of high K(+), characterized by slow onset due to postsynaptic current summation. Enhancing GABAergic transmission by pentobarbital surprisingly accelerated the high-K(+) rhythm of control cells (though depressing background activity), whereas it slowed it down in chronically treated cells. This contrasting effect of pentobarbital suggests that, to preserve bursting ability, chronic slices developed a distinct GABAergic inhibitory control on over-expressed bursting circuits. Conversely, in control slices GABAergic transmission depressed spontaneous activity but it facilitated bursting frequency. Thus, even after homeostatic rearrangement, developing mammalian spinal networks still generate rhythmic activity.

1. The well-developed cytoarchitecture of rat organotypic spinal cord culture makes it a suitable model to explore how persistent suppression of certain synaptic inputs might be compensated by increased synaptic efficacy (homeostatic plasticity). 2. Spontaneous or electrically evoked synaptic transmission of patch-clamped ventral horn interneurons was studied in control solution after blocking, for the second week in culture, AMPA/kainate receptors with CNQX or glycine and GABAA receptors with strychnine and bicuculline, or indiscriminately removing inputs with tetrodotoxin (TTX). 3. In untreated cells, spontaneous postsynaptic currents (PSCs) had fast (tau < 5 ms) or slow (tau > 10 ms) decay. A similar separation was observed when recording miniature currents (mPSCs). Slow decay PSCs were suppressed by strychnine plus bicuculline while fast decay events were eliminated by CNQX. 4. After chronic CNQX treatment the frequency of spontaneous, fast PSCs (of larger amplitude) or mPSCs was almost doubled with respect to control. These events were blocked by acutely applied CNQX, which unmasked slow PSCs. 5. After chronic TTX treatment neither the frequency nor the amplitude of spontaneous events was changed. 6. After chronic strychnine and bicuculline treatment the frequency and amplitude of all PSCs was decreased in most cells. mPSCs were also decreased in frequency. Spontaneous or electrically evoked currents acquired a larger component mediated by NMDA receptor activity. 7. The developing spinal network thus operated distinct homeostatic processes which led to strong enhancement in glutamatergic transmission after CNQX block or to broad downregulation of synaptic activity following chronic exposure to strychnine and bicuculline.

1. In the presence of certain excitatory substances the rat isolated spinal cord generates rhythmic oscillations believed to be an in-built locomotor programme (fictive locomotion). However, it is unknown whether a long-term culture of the same tissue can express rhythmic activity. Such a simplified model system would provide useful data on the minimal circuitry involved and the cellular mechanisms mediating this phenomenon. For this purpose we performed patch clamp recording (under whole-cell voltage or current clamp conditions) from visually identified ventral horn interneurones of an organotypic slice culture of the rat spinal cord. 2. Ventral horn interneurones expressed rhythmic bursting when the extracellular [K+] was raised from 4 to 6-7 mM. Under voltage clamp this activity consisted of composite synaptic currents grouped into bursts lasting 0.9 +/- 0.5 s (2.8 +/- 1.5 s period) and was generated at network level as it was blocked by tetrodotoxin or low-Ca2+-high-Mg2+ solution and its periodicity was unchanged at different potential levels. 3. In current clamp mode bursting was usually observed as episodes comprising early depolarizing potentials followed by hyperpolarizing events with tight temporal patterning. Bursting was fully suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and reduced in amplitude and duration by N-methyl-D-aspartate (NMDA) receptor antagonism without change in periodicity. Extracellular field recording showed bursting activity over a wide area of the ventral horn. 4. Regular, rhythmic activity similar to that induced by K+ also appeared spontaneously in Mg2+-free solution. The much slower rhythmic pattern induced by strychnine and bicuculline was also accelerated by high-K+ solution. 5. The fast and regular rhythmic activity of interneurones in the spinal organotypic culture is a novel observation which suggests that the oversimplified circuit present in this culture is a useful model for investigating spinal rhythmic activity.

Objective: To detect changes of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) at different stages of recovery from severe brain injury and to determine whether they can be used to predict late functional outcome., Design: Correlational study on a prospective cohort., Setting: Brain injury rehabilitation center., Patients: Twenty-seven consecutively sampled patients with severe traumatic brain injury referred to the inpatient intensive rehabilitation unit of primary care in a university-based system., Main Outcome Measures: (1) Glasgow Outcome Scale, Disability Rating Scale, and Functional Independence Measure; (2) SEPs and MEPs from upper limbs (ULs) and lower limbs (LLs). Outcome was assessed at 6 and 12 months after trauma. Correlations were computed with the nonparametric test of Spearman-Rank., Results: Both SEPs and MEPs showed dynamic changes (p < .02 for N20, p < .05 for N30, P40, and N45), with a trend toward a progressive normalization. N30 was more frequently abnormal than N20. SEPs from LLs were more frequently and more persistently abnormal than those from ULs. Clinical and functional outcome was strongly correlated with the degree of abnormality of SEPs from LLs (p < .002), whereas only mild relationships were found with SEPs from ULs. Both SEPs and MEPs showed a high negative predictive value (83% for N30 and 83% for P40), but only SEPs from LLs also had a high positive predictive value (72% for P40). Sensitivity was 88% both for N30 and P40. Specificity was 50% for N30 and 70% for P40)., Conclusion: SEPs from LLs can be very useful in monitoring the postacute phase of traumatic brain injury and in identifying patients who require further intensive rehabilitation. MEPs may be of questionable value.

Organotypic cocultures of dorsal root ganglia and spinal cord from embryonic rats provides direct access to spinal interneurons in a culture system in which the cytoarchitectural organization of the spinal cord slice is maintained. This preparation was used to investigate the possible induction of rhythmic behaviour at different times of development in vitro. Spontaneous rhythmic bursts induced by coapplication of strychnine (1 microM) and bicuculline (20 microM) were observed with patch-clamp recordings from ventral interneurons. Ventral horn interneurons consistently developed a very regular pattern of activity which was superimposed on a background of sustained synaptic activity. The pattern of the spontaneous bursting following application of strychnine and bicuculline showed a developmentally regulated difference in frequency between two distinct stages of in vitro development.

Objective: To detect the effect of a strenuous exercise on equilibrium and to quantify its time course., Participants and Methods: Body sway area, sway path, and center of foot pressure were recorded in eight young able-bodied subjects, standing quietly with feet together, with eyes open (EO) and eyes closed (EC), on a dynamometric platform, before and after treadmill walking for 25min, during which subjects approached the maximum heart rate., Results: A significant increase in body sway was observed after exercise. It was present under both visual conditions and affected both sway area and sway path. Sway increased most in the initial few minutes (sway area EO=800.7mm2 [p < .005], EC=1,779.5mm2 [not significant]; sway path EO=545mm [p < .0001], EC=811.8mm [p < .05]) with respect to preexercise values (sway area EO=449.4mm2, EC=1,316.2mm2; sway path EO=369.5 mm, EC=652.5mm) and was followed by a plateau (sway area EO=609.9mm2, EC=1,567.9mm2; sway path EO=431.2mm, EC=710.9mm). Full recovery to basal values occurred within about 15min after the end of the exercise., Conclusions: Body sway is affected by prolonged fatiguing exercise, such as strenuous walking. This effect is of moderate extent and vanishes within a few minutes.

During upright stance, foot dorsiflexion induced by the movement of a supporting platform elicits a short- (SLR) and a medium-latency response (MLR) in both the soleus and the flexor digitorum brevis muscles; foot plantarflexion elicits a MLR in the tibialis anterior. The SLR is the counterpart of the stretch reflex, but no general agreement exists about the origin of the MLR, though recent results suggest that it is transmitted through group II afferent fibres. Animal studies have shown that group II fibres impinge on interneurones projecting contralaterally as well as ipsilaterally, whereas group I fibres impinge on interneurones which project mainly ipsilaterally. Therefore, we compared the changes in amplitude and latency of the SLRs and MLRs in the right and left limb during postural perturbations induced while subjects maintained both feet on the platform (both-on condition) or while they maintained only one foot on the platform and the other on firm ground (one-on condition). Under the both-on condition, the pattern of EMG responses described above occurred bilaterally. Under the one-on condition, both SLRs and MLRs occurred in the displaced leg. However, whereas the SLRs did not change in amplitude compared with the both-on condition, the MLRs decreased in amplitude to about 50%. MLRs were also present in the non-displaced leg. They were not preceded by any SLR but showed a further decrease in size with respect to the corresponding responses in the perturbed leg. Latency of the MLRs of the perturbed leg increased by about 5 ms passing from the both-on to the one-on condition. In the latter condition, a further increase of 5 ms was observed in the nonperturbed leg with respect to the displaced one. The occurrence of the MLRs but not of the SLRs in the contralateral non-displaced leg is in keeping with the notion that crossed neural pathways fed by spindle group II afferent fibres subserve the MLRs. The changes in latency of the MLRs under the one-on condition compared with both-on give a cue about the synaptic delays along the neural circuit and the time taken by the afferent impulses to cross the spinal cord.

Body sway was studied at various body inclinations, voluntarily maintained for about 1 min, in young and elderly normals and in idiopathic parkinsonians. They stood on a dynamometric platform, whose output gave the instantaneous centre of foot pressure (CFP), its mean value and body sway area, with eyes open (EO) or closed (EC). Subjects held the normal upright stance, or the maximum possible inclined posture (body straight, rotated at the ankle joints) in forward or backward direction, or intermediate postures. EMG was recorded from tibialis anterior (TA), soleus (Sol), extensor digitorum brevis (EDB) and flexor digitorum brevis (FDB). The cross-correlation function between the profile of the EMG envelope and the profile of the shift of CFP along the sagittal plane was calculated. In young subjects standing with EO, the maximum extent of antero-posterior (A-P) displacement of CFP was about 60% of foot length. EC reduced this value to about 50%. In the elderly normals, the maximum A-P displacement was about 40% (EO) and 30% (EC). In both groups, sway area was minimal during normal stance with EO and increased progressively when the subjects leant forward or backward. With EC, sway area further increased during normal stance and the rate of increase in relation to inclination augmented markedly. Sol was tonically active during normal stance. Forward leaning increased Sol EMG and induced activity in FDB. TA and EDB were active during backward leaning. The peak of the cross-correlation function between Sol EMG and instantaneous CFP was higher during normal stance than forward inclination, while the reverse was true for FDB. This suggests a role of FDB in the fine-tuning of postural adjustment during forward leaning, and a weight-supporting role of Sol. During backward inclination, TA but not EDB was cross-correlated with CFP. In the parkinsonians, maximum A-P displacement of CFP was just about 30% of foot length (EO; about 20% with EC); its extent was inversely correlated with the severity of the disease. The relationship between sway area and A-P displacement was similar to the elderly, both with EO and EC, within the common range of inclination. In the patients affected by the long-term syndrome, A-P displacement was further reduced while sway area increase at the critical postures was often absent. In all patients, the relationship between muscle activity and body inclination was comparable to normal.(ABSTRACT TRUNCATED AT 400 WORDS)

This work focuses on the neurophysiological features in a patient with action myoclonus and mental deterioration following methylbromide intoxication. The patient is a 28-year-old man, without respiratory distress or exposure to other toxics. Myoclonus improved with polytherapy (clonazepam, 5-HT, carbidopa, GABA). The neurophysiological and neuropsychological evidence in this patient suggests a possible double site of action of methylbromide at cortical and subcortical levels.

Through the use of a feedback-controlled dextrose infusion system, we obtained continuous monitoring of the blood glucose level in a patient undergoing surgery for multiple pancreatic beta-cell tumors. In addition, this device infused dextrose at variable rates to maintain a predetermined euglycemic level of 90 mg/dl. Before locating the source of excessive insulin production, the maximum dextrose infusion rate of 400 mg/min was required; but after extirpation of multiple insulinomas, the dextrose-infusion rate declined whereas the blood glucose level rose above the preselected level. These results emphasize the usefulness of a monitoring and infusion system not only in protecting the patient from the hazard of hypoglycemia under anesthesia but also as an aid in determining whether all insulin-secreting tumors have been removed.

A novel method for localization of abnormal parathyroid glands involving color-processing of nuclear scintigrams of the neck after injection of Thallium-201 and Technetium pertechnetate is presented with surgical correlation. Preoperative localization of single parathyroid adenomas was successful in 88% of previously unoperated patients and in 85.7% of those with adenomas not located at previous surgery. Eighty-three per cent of glands with secondary hyperplasia, 66% of glands with primary hyperplasia, and one carcinoma were localized. No abnormal studies were seen in non-hyperparathyroid hypercalcemia, and no false positive studies were seen. Localization appeared related to larger adenomas (300-5000 mg), although one of 60 mg was localized. Color-comparison dual-isotype scintigraphy was useful for localization of parathyroid adenomas and hyperplastic glands and exceeded the reported sensitivity of either ultrasonography or computerized tomography. It deserves wider evaluation in preoperative management of at least hyperparathyroidism of the primary or persistent types.

The treatment of clear cell adenocarcinoma of the cervix and vagina in young women has varied widely from one institution to another. Since 1956, 16 such patients have been treated primarily with radical surgery at the University of California, San Francisco. The operations have ranged from radical hysterectomy and bilateral pelvic lymph node dissection with preservation of the ovaries to total pelvic exenteration, depending upon the location and extent of the disease. Vaginal reconstruction has been carried out in most of the patients who required vaginectomy. Eleven of the 16 patients are living and well. The remaining five have died of disease, two of them after relatively long disease-free intervals.

Forty patients with medullary thyroid carcinoma and 3 patients with C-cell hyperplasia were studied. Seventeen (40%) cases were sporadic and 26 (60%) were hereditary. Eight patients had type lla multiple endocrine neoplasia, 7 patients had type llb multiple endocrine neoplasia, and 11 patients had familial nonmultiple endocrine neoplasia medullary thyroid carcinoma. Mean follow-up was 6.3 years, with actuarial survival of 88% and 78% at 5 and 10 years (22 and 13 patients), respectively. Seven patients died 1.5 to 10 years after the initial operation; all had advanced disease at presentation (6 with distant, 1 with lymph node metastasis). No deaths occurred in patients with familial nonmultiple endocrine neoplasia medullary thyroid carcinoma, C-cell hyperplasia, or medullary thyroid carcinoma limited to the thyroid gland. Nineteen (68%) of 28 patients diagnosed without screening had regional or distant metastases, whereas only 6 (40%) of 15 patients diagnosed by screening had metastases. Twenty-six patients treated initially with total thyroidectomy and central neck clearance required an average of one reoperation, whereas those with lesser initial procedures required an average of two reoperations. We concluded that (1) familial nonmultiple endocrine neoplasia medullary thyroid carcinoma, early medullary thyroid carcinoma or C-cell hyperplasia, and asymptomatic patients have a good prognosis; (2) screening for medullary thyroid carcinoma by measuring serum calcitonin levels results in earlier diagnosis; and (3) total thyroidectomy and central neck clearance is the procedure of choice for medullary thyroid carcinoma.

The three mitochondrially translated ATP synthase subunits of Saccharomyces cerevisiae were extracted from the enzyme and from whole mitochondria using an organic solvent mixture and then purified by reverse-phase HPLC. The amino acid composition of subunit 6 is close to the one predicted from the oli2 gene. The partial amino terminal sequence of subunit 6 reveals a post-translational cleavage site between the Thr-10 and Ser-11 residues of the precursor. Thus, mature subunit 6 contains 249 amino acid residues and displays a molecular mass of 27943 Da.

In the embryo of Xenopus laevis, adenylate cyclase activity is higher in the chorda-mesoderm than in the endoderm. The peak of activity in the chorda-mesoderm is observed at the beginning of the migration of the primordial germ cells (PGC). There could be a correlation between the adenylate cyclase activity of the chorda-mesoderm and the intraendodermic migration of the PGC.

Fifty hemiparetic subjects were selected from a population of 250 patients according to criteria forsuitable candidates for peroneal stimulation. The patients received from 10 to 120 hours of treatment during 2--5 weeks. The therapeutic results obtained were classified into four groups, ranging from none to excellent improvement of voluntary movement and reduction of spasticity. The clinical results were correlated to different variables where time from lesion, spasticity, and extent of treatment appeared to be the most important ones. The percentage of excellent results decreased with increasing time from lesion and spasticity, and increased with increasing treatment. Orthotic validity (i.e. the beneficial effect of the orthosis) was observed in 76% of the selected cases and in most of them it was very significant. Preliminary tests performed on 9 subjects showed that in cases with orthotic validity the peroneal brace slightly reduces the oxygen consumption of patients and improves their motivation. This work gives a more quantitative perspective of the validity of functional peroneal stimulation and a better indication of criteria for patient selection. The overall validity of an electronic peroneal brace appears to apply to 15% of the total ambulatory hemiparetic population and its therapeutic value is relevant in two-thirds of such cases if sufficient treatment is provided. Application of functional electrical stimulation to non-ambulatory subjects in the acute phase may however lead to a higher percentage of cases of therapeutic validity.

A 1H-naphtho[2,1-b]pyran derivative (K 8409) has undergone pharmacological investigation for psychotropic activity. The results show potential antidepressant action quantitatively similar to that of imipramine and amitriptyline, but due rather to MAO inhibition than to imipramine-like activity; interestingly enough, anti-MAO activity was particularly selective for the serotonin-converting enzyme, both centrally and peripherally. The outcome of the other tests suggests that the incidence of untoward effects is likely to be limited.

One subunit of the membrane portion of yeast ATP synthase was purified. Structural data are reported. This subunit (subunit 4) is the fourth polypeptide of the complex when classifying subunits in order of decreasing molecular mass. Its apparent relative molecular mass is about 25,000. The polypeptide was extracted from the complex with a mixture of chloroform/methanol (1/1) and 0.5 M pyridinium acetate pH 6.0. Purification was performed with a combination of gel permeation chromatography on Sephadex G-75 and high-performance gel permeation chromatography with aqueous solvents containing 5% sodium dodecyl sulfate. The amino acid composition is reported here. The following sequence of the NH2-terminal ten residues was determined: Met-Ser-Ser-Thr-Pro-Glu-Lys-Gln-Thr-Asp.

Sixteen consecutive patients with the clinical diagnosis of hyperparathyroidism, nine with and seven without previous surgery, had computed tomography (CT) examinations preoperatively to evaluate the use of CT in localizing parathyroid adenomas. The patients were scanned at 5 mm intervals from the level of the hyoid bone to the lung apex. Scanning of the mediastinum was performed at 10 mm intervals from apex to lung base. Computed tomography correctly identified prospectively the site of the adenoma in 10 of 13 patients (77%), with surgically proven adenomas. In retrospect, all 13 adenomas could be identified. One false positive diagnosis of adenoma was made. Our study suggests that CT may be beneficial in the preoperative localization of parathyroid tumors, particularly in ectopic locations.

The structure of ATP synthase subunit 4 was determined by using the oligonucleotide probe procedure. This subunit is the fourth polypeptide of the complex when classifying subunits in order of decreasing molecular mass. Its relative molecular mass is 25 kDa. The ATP4 gene was isolated and sequenced. The nucleotide sequence predicts that subunit 4 is probably derived from a precursor protein 244 amino acids long. Mature subunit 4 contains 209 amino acid residues and the predicted molecular mass is 23250 kDa. Subunit 4 shows homology with the b-subunit of Escherichia coli ATP synthase and the b-subunit of beef heart mitochondrial ATP synthase. By using homologous transformation, a mutant lacking wild subunit 4 was constructed. This mutant is devoid of oxidative phosphorylation and F1 is loosely bound to the membrane. Our data are in favor of a structural relationship between subunit 4 and the mitochondrially-translated subunit 6 during biogenesis of F0.

The authors review the different stages of hemiplegic rehabilitation, the aims of kinesitherapy, the principal techniques of neuromotor rehabilitation (Kabat, Bobath, Perfetti) and the use of mechanical or electronic aids, to compensate motor handicaps persisting at the end of rehabilitation treatment.

The metabolic manifestations and operative findings in 10 patients with a diagnosis of parathyroid carcinoma were analyzed to determine whether they differ from those in patients with parathyroid adenomas and similar degrees of hypercalcemia. Two groups of patients with parathyroid adenomas were used for comparison. Group A consisted of eight patients with "atypical" benign adenomas (mean preoperative level of serum calcium: 13.4 mg/dl); group B consisted of 13 patients with benign typical adenomas--all with preoperative serum calcium levels greater than or equal to 13.0 mg/dl (mean: 14.2 mg/dl). The patients with carcinoma (mean preoperative level of serum calcium: 15.3 mg/dl) had a frequency of osteoporosis and osteitis fibrosa cystica (50%) comparable with that of group A (33%) and group B (62%). Seventy percent of the patients with carcinoma had renal disease (nephrolithiasis, nephrocalcinosis, or impaired renal function), whereas only 38% of group A and 15% of group B had similar disorders. The patients with carcinomas had the highest frequency of combined bone and renal disease (50% versus 14% in group A and 15% in group B). Anemia, peptic ulcer disease, and hypertension occurred with similar frequencies in the three groups. Three patients with recurrent parathyroid carcinoma died of profound hypercalcemia, renal failure, or cardiac arrhythmia. In general, although patients with parathyroid carcinomas have more profound metabolic abnormalities than do patients with primary hyperparathyroidism, the metabolic manifestations in patients with parathyroid carcinoma are comparable with those in patients with parathyroid adenomas and profound hypercalcemia. Furthermore atypical adenomas share many anatomic and histopathologic features with parathyroid carcinomas, and distinguishing between the two is sometimes possible only in cases of tumor recurrence.

From 1950 to 1973, 129 patients received irradiation for esophageal squamous-cell carcinoma at the University of California, San Francisco. From this group, 26 received surgical and irradiation treatment. Twelve did not receive irradiation until recurrence became evident and among them were no 5-year survivors. Among the other 14 were six 5-year survivors (43%). The authors believe that planned sequential irradiation and surgery offer the best chance for cure in squamous-cell carcinoma of the esophagus. Selection factors, treatment details, and therapeutic regimens are presented and a management plan proposed for this group of operable patients.

Impairment of adrenal function is a great hazard to patients undergoing major operation. The most important adrenal steroids are glucocorticoids (hydrocortisone), 17-ketosteroids, mineralo-corticoids (aldosterone), and small amounts of estrogen and progesterone. Urinary output of 17-hydroxycorticoids reflects overall adrenal cortical activity. Under severe stress this output increases greatly. Adrenal replacement therapy is facilitated by the advent of more powerful and more soluble adrenal hormone derivatives. Hydrocortisone hemisuccinate sodium is the agent of choice in surgical emergencies and for management of bilateral adrenalectomy. Fatal adrenal crisis may develop during operation in patients receiving hydrocortisone for long periods of time. Hydrocortisone may be of help in unresponsive shock not due to loss of blood. The usual side effects of the corticoids can be controlled easily.