Colorectal cancer with indeterminate pulmonary nodules.

Colorectal cancer (CRC) is one of the most common malignancies with a dismal prognosis. Indeterminate pulmonary nodules (IPNs) are lung nodules with uncertain nature, generally defined as a noncalcified nodule smaller than 10 mm in diameter or solid nodule no greater than 20 mm at maximum diameter without malignant character. With the widespread use of preoperative staging computed tomography (CT) of the chest and follow-up CT, IPNs are frequently detected in patients with CRC, which makes diagnosis more controversial. Generally, progression to pulmonary metastasis from IPNs is rare. Thus, no further interventions were needed for IPNs in CRC patients. A second reviewing of scans with IPNs by both clinicians and experienced thoracic radiologists may help to obtain a more accurate diagnosis.

Use of a two-way non-rebreathing valve to simplify the measurement of twitch mouth pressure using an inspiratory pressure trigger and the establishment of an optimal trigger threshold for healthy subjects and COPD patients.

OBJECTIVE: Controlled twitch mouth pressure (Tw Pmo) via the use of a two-way non-rebreathing valve is a new method to assess diaphragm contractility. The optimal trigger threshold was confirmed. DESIGN: We sought to determine the optimal trigger threshold for 17 healthy subjects (29±4 years) and 17 COPD patients (64±10 years). The Tw Pmo, twitch oesophageal pressure (Tw Pes) and twitch transdiaphragmatic pressure (Tw Pdi) in response to phrenic nerve stimulation were measured using an inspiratory pressure trigger at -1, -2, -3, -4, -5 and -6 cmH2O. RESULTS: The lung volume did not change during triggering at different trigger thresholds using a two-way non-rebreathing valve. The highest correlation between Tw Pmo and Tw Pes in healthy subjects and COPD patients occurred for a -2 cmH2O trigger threshold (r=0.939 and r=0.869, P<0.0001). The narrowest limits of agreement for Tw Pmo and Tw Pes both occurred at -2 cmH2O in healthy subjects, with a bias (range) of -0.4 cmH2O (-1.85 to 1.41), and in COPD patients, with a bias (range) of 0.1 6cmH2O (-1.36-1.67). CONCLUSIONS: We conclude that the measurement of Tw Pmo using a two-way non-rebreathing valve is of clinical value to investigate the suspected diaphragm contractility. The highest trigger threshold for clinical applications was -2 cmH2O.

Early demyelination of primary A-fibers induces a rapid-onset of neuropathic pain in rat.

Some types of peripheral neuropathic pain are associated with damage to myelin rather than to axons of primary sensory neurons. It is extremely important to develop selective demyelination animal models for understanding neuropathic pain caused by demyelination. We induced a rapid-onset and reversible demyelination of peripheral A-fibers and neuropathic pain behaviors in adult rats by a single injection of cobra venom into the sciatic nerve. The relation between A-fiber demyelination and the abnormal pain behaviors was investigated using this model. Microfilament recordings revealed that cobra venom selectively blocked A-fibers, but not C-fibers. Selective blockade of A-fibers may result from A-fiber demyelination at the site of venom injection as demonstrated by microscope examination. The axons of the demyelinated A-fibers appeared to be otherwise normal. Neuropathic pain behaviors appeared almost immediately after venom injection and lasted about 3 weeks. Electrophysiological studies indicated that venom injection induced loss of conduction in A-fibers, increased sensitivity of C-polymodal nociceptors to innocuous stimuli, and triggered spontaneous activity from both peripheral and central terminals of C-fiber nociceptors. Neurogenic inflammatory responses were also observed in the affected skin via Evan's Blue extravasation experiments. Both antidromic C-fiber spontaneous activity and neurogenic inflammation were substantially decreased by continuous A-fiber threshold electric stimuli applied proximally to the venom injection site. The data suggest that normal activity of peripheral A-fibers may produce inhibitory modulation of C-fiber polymodal nociceptors. Removal of inhibition to C-fiber polymodal nociceptors following demyelination of A-fibers may result in pain and neurogenic inflammation in the affected receptive field.

An Acupuncture-like Quantitative Mechanical Stimulator.

A stimulator that analogs the needle puncture has been designed to deliver quantitative mechanical stimulus to a small area of muscle. A friction coupler is designed to transmit the driving force from motor to a needle which is used to deliver stimulus. Rotation of the needle may be stopped but the friction will be maintained between the needle and the tissue when this friction moment comes to the driving moment of the coupler. Experiments were done on 6 hindlimb muscles in 2 cats and the results show the value of the stimulator in probing the mechanisms of acupuncture.

[Morphological and physiological changes of the nervous system in chronic painful peripheral neuropathy].

Peripheral nerve injury may result in many kinds of sensory disorders such as hyperalgesia, dysesthesia, causalgia, etc. This paper mainly reviews the changes in morphology and physiological function occuring in the chronic painful peripheral neuropathy of two kinds of animal models which are now generally used to study the mechanisms of chronic neuropathic pain.

Inhibitory effect of anisodamine on the neuropathic hyperalgesia following peripheral nerve injury (II).

A peripheral neuropathy with hyperalgesia and allodynia was produced by loosely tying constrictive ligature around the left sciatic nerve of rats, i.v. injection of anisodamine 20 mg/Kg abolished both neuropathic hyperalgesia responses to noxious radiant heat and ectopic discharges generated from the injured region of the nerve. Anisodanime applied either systemically or locally to the damaged area of the nerve not only ceased the spontaneous ectopic discharges recorded from A beta to C fibers but also blocked the afferent ectopic discharge elicited by K+ channel blocker, noradrenaline, Ca2+ or antidromic stimulation of sciatic nerve proximal to the injured nerve area. The experiments indicated that anisodamine probably possessed a calcium channel blocker-like activity and produced selective block of the new channels in the injured area. It is suggested that anisodamine may be a candidate therapeutic agent in relieving hyperalgesia and allodynia following nerve injury.

The relationship between new ion channels and ectopic discharges from a region of nerve injury.

Changes in ectopic discharges from axons in an injured nerve were examined while agents that interact with ion channels were applied to the site of the nerve injury. Tetraethylammonium (TEA) greatly facilitated spontaneous ectopic discharges or evoked ectopic firing in previously silent axons. Tetrodotoxin, an Na+ channel blocker, completely blocked spontaneous discharges. Verapamil, La3+, and Mn2+, agents that interact with Ca2+ channels, blocked spontaneous discharges and depressed the responses evoked by TEA, noradrenaline and high concentration of K+. Increasing Ca2+ levels facilitated ectopic discharges and this effect was blocked by La3+ and Mn2+. Normal axons (from uninjured nerves) were insensitive to all the effects seen in the axons from the injured nerve. These results suggest that following nerve injury the membrane of the regenerating sprout contains new ion channels, particularly Ca2+ channels, and that these channels are responsible for the generation of ectopic discharges.

Effects of m-nisoldipine and nisoldipine on electric activity of human atrial tissue.

Using intracellular microelectrode technique and microcomputer analyzing system, the effects of m-nisoldipine (m-Nis) and nisoldipine (Nis) on spontaneous electric activity of human atrial tissue were studied. APA and Vmax were remarkably decreased by m-Nis (0.25 and 1.25 mumol.L-1) and Nis (0.25 mumol.L-1). RPF was also greatly decreased as a result of inhibition in VDD. The inhibitory effects of m-Nis on transmembrane potentials were less than those of Nis at equal concentration (0.25 mumol.L-1). Neither MDP nor APD90 was affected by m-Nis and Nis.

Intracellular records of the effects of primary afferent input in lumbar spinoreticular tract neurons in the cat.

1. The afferent-evoked synaptic input to lumbar spinal cord (L5-S1) neurons that were activated antidromically from the medial pontomedullary reticular formation (nucleus reticularis gigantocelluaris and vicinity) was investigated with the use of intracellular recordings in pentobarbital sodium-anesthetized cats. 2. Spinoreticular tract (SRT) neurons (n = 33) were categorized into three types ("deep-inhibited," "deep-complex," and "intermediate") on the basis of their locations and of their responses to natural and electrical stimulation. 3. The deep-inhibited-type neurons, located in the medial part of the deeper laminae (approximately VI-VIII), comprised a large component of the sample (20/33). They had no demonstrable excitatory receptive field (RF). However, electrical stimulation of low-threshold cutaneous afferents of hindlimb nerves evoked inhibitory postsynaptic potentials (IPSPs) via an oligosynaptic linkage. High-threshold cutaneous and muscle afferents also evoked IPSPs. 4. In the deep-complex-type neurons (8/33), electrical stimulation of low-threshold cutaneous afferents evoked complex IPSP-excitatory postsynaptic potential (EPSP) sequences. With intense stimuli, long-latency C-fiber-like EPSPs were evoked. Two of these eight neurons were characterized as wide-dynamic-range (WDR) neurons with large, excitatory and inhibitory cutaneous RFs. 5. Intermediate-type neurons (5/33) were concentrated in the lateral spinal gray and relatively superficially (approximately lamina V). These neurons had convergent low- and high-threshold cutaneous inputs (WDR neurons). Electrical stimulation of low-threshold cutaneous afferent fibers from within the excitatory RF evoked mono- or disynaptic EPSPs followed by IPSPs. High-threshold muscle and cutaneous afferents also evoked EPSPs. 6. These results show that SRT neurons have a variety of response characteristics resulting from various degrees of spatial and temporal summation of primary afferent input. Neurons with widespread inhibitory responses but no excitatory drive from the periphery comprise a surprisingly large component of the SRT: the function of these cells is unknown. It is apparent that the spinoreticular projection has considerable functional heterogeneity.

Electrophysiological evidence for hyperalgesia in the peripheral neuropathy.

A peripheral neuropathy was produced in adult rats by placing loosely constrained ligature around the common sciatic nerve. At the ligature region of the nerve, demyelination developed. The postoperative behavior of these rats indicated that hyperalgesia and allodynia were produced. The electrical activity pattern of the damaged fibers was remarkably different from those of normal nerves: there were some abnormal spontaneous afferent firings from the injured fibers; multi-impulse responses of C-fiber to single shock was recorded; a lasting firing was elicited after the injured region was gently pressed or by oil drops at 40 degrees C; an antidromic electric stimulus to the injured region, stimulations of L5 sympathetic ganglion or systemic administration of noradrenaline, all caused an increase in on-going spontaneous discharges of the injured fibers or brought the silent fibers into firing. Stimulation of the dorsal roots of the sciatic nerve produced no effect on their activities or caused a pause of the on-going discharges of them. Phentolamine, an alpha receptor blocker, ceased the abnormal firing, but did not affect the normal fiber firings. It is hypothesized that noradrenaline released by the sympathetic nerve would be an important factor responsible for both hyperalgesia and allodynia following injury of peripheral nerve.

A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man.

A peripheral mononeuropathy was produced in adult rats by placing loosely constrictive ligatures around the common sciatic nerve. The postoperative behavior of these rats indicated that hyperalgesia, allodynia and, possibly, spontaneous pain (or dysesthesia) were produced. Hyperalgesic responses to noxious radiant heat were evident on the second postoperative day and lasted for over 2 months. Hyperalgesic responses to chemogenic pain were also present. The presence of allodynia was inferred from the nocifensive responses evoked by standing on an innocuous, chilled metal floor or by innocuous mechanical stimulation, and by the rats' persistence in holding the hind paw in a guarded position. The presence of spontaneous pain was suggested by a suppression of appetite and by the frequent occurrence of apparently spontaneous nocifensive responses. The affected hind paw was abnormally warm or cool in about one-third of the rats. About one-half of the rats developed grossly overgrown claws on the affected side. Experiments with this animal model may advance our understanding of the neural mechanisms of neuropathic pain disorders in humans.

Effect of gossypol on the potential difference of rat seminiferous tubules.

The p.d. of the rat seminiferous tubules was 4.75 +/- 1.39 mV (lumen negative) at 35 degrees C and varied linearly with temperatures from 26 to 40 degrees C. A depolarization of the seminiferous tubules was found in the rats administered with gossypol at the dosage of 30 mg/kg body weight for 3 weeks, the p.d. lowered to 3.63 +/- 0.79 mV at 35 degrees C and was independent of the changes of seminiferous tubules temperature. In the 5-week-gossypol-treatment group, the tracer penetrated not only the myoid cell layer, but also went beyond the tight junction complexes between Sertoli cells. The lanthanum appeared in the cleft surrounding spermatogonia. In the 8-week-gossypol-treatment group, the lanthanum was found in the adluminal compartment. It indicates that gossypol can cause a dysfunction of the Sertoli cells and blood-testis barrier and disturb a good physiological environment for the developing spermatocytes.

Further investigation on the hypothesis of meridian-cortex-viscera interrelationship.

The hypothesis of Meridian-Cortex-Viscera Interrelationship maintains: 1. Meridian channel system is an independent system connected with the nerves to the cortex; 2. It acts through the nerves; 3. The nervous action is realized by humoral agents. This article gives preliminary-experimental supports for the above criteria.

Influence of monoaminergic nuclei in lower medulla and their neurotransmitters on the activity of nociceptive units in spinal cord.

In this article, seventy nociceptive units of dorsal horn and five preganglionic sympathetic units of spinal cord in forty-four anesthetized cats immobilized with Flaxedil were studied. The results observed were: 1. Electrophoretic administration of noradrenaline (NA) induced a remarkable depression of both evoked and spontaneous discharges of nociceptive units. Similar effects could be produced by electric stimulation of noradrenergic Al nuclei or injection of amphetamine or hand pressing of "Zusanli" (one form of acupuncture) respectively. 2. The effect of 5-hydroxytryptamine (5-HT on evoked nociceptive discharge was similar to NA, but on spontaneous discharge of nociceptive units was excitement. 3. Effects of the above-mentioned factors on the nociceptive discharges of preganglionic sympathetic neurons were similar to the nociceptive units too. 4. On the contrary, the activity of inhibited neuron by noxious stimulation was augmented by administration of NA, amphetamine, the stimulation of Al nuclei and the deep muscle. It is suggested that the noradrenergic nuclei in lower brain stem may play an important role in descending inhibitory circuits of nociceptive spinal reflex.