The release of beta-endorphin and the neuropeptide-receptor mismatch in the brain.

Microprobes bearing immobilized antibodies to the carboxy-terminus of beta-endorphin were used to study the release of beta-endorphin in the urethane anaesthetized rat following electrical stimulation of the ipsilateral arcuate nucleus. The microprobes were inserted through the cerebral hemisphere, the superior colliculus and the midbrain periaqueductal grey. Since such microprobes detect extracellular molecules along their entire length they give information on the persistence and spread of compounds following release. Little immunoreactive-beta-endorphin was detected in the areas of brain sampled during electrical stimulation of arcuate nucleus but a remarkable spread throughout the midbrain and cerebral cortex occurred within 30 min of the cessation of stimulation. The results suggest that although beta-endorphin-containing fibres are absent in many parts of the brain, this neuropeptide can access receptors in these sites and it is not necessary for release to be directly adjacent to opiate receptors. As such it is important evidence supporting the hypothesis of volume transmission as a means of neuronal communication. The results also suggest that an important mechanism of the transport of beta-endorphin is the cerebrospinal fluid.

Spontaneous release of immunoreactive neuropeptide Y from the central terminals of large diameter primary afferents of rats with peripheral nerve injury.

Microprobes bearing immobilized antibodies to the C-terminus of neuropeptide Y were used to measure the release of this neuropeptide in the spinal cords of rats with a unilateral peripheral neuropathy and in sham-operated animals. All neuropathic animals showed the characteristic behavioural syndrome and were studied at 14 days postsciatic nerve loose-ligation. An extensive spontaneous release of immunoreactive neuropeptide Y was detected in the spinal cords of the neuropathic rats and, compared to sham-operated rats, a new zone of release was found in the deep dorsal horn. Electrical stimulation of large diameter primary afferents proximal to the nerve ligature produced widespread release of neuropeptide Y in the dorsal horn which persisted for up to 1 h poststimulation. It is possible that ectopic impulses arising in the injured nerve were responsible for the spontaneous central release of neuropeptide Y and this neuropeptide may play a role in the central response to peripheral nerve injury.

The effect of a peripheral mononeuropathy on immunoreactive (ir)-galanin release in the spinal cord of the rat.

The pattern of ir-galanin release in the spinal cord of rats with a peripheral mononeuropathy was studied. On the side of the cord ipsilateral to the nerve injury enhanced ir-galanin release was found in the superficial dorsal horn. It is probable that, after nerve injury, some primary afferent neurons spontaneously release galanin from their central terminals.

The release of immunoreactive neuropeptide Y in the spinal cord of the anaesthetized rat and cat.

The release of immunoreactive (ir-) neuropeptide Y (NYP) was studied in the anaesthetized rat and cat by means of microprobes bearing immobilized antibodies to the C terminus of NPY. An extensive basal release of ir-NYP was detected throughout the dorsal and upper ventral horn of the rat. This spontaneous release was not significantly altered by sectioning the spinal cord at the thoraco-lumbar junction nor by electrical stimulation of peripheral nerves. Since NPY is virtually absent in primary afferents it is probable that spontaneous release within the spinal cord comes from active NPY-containing intrinsic spinal neurones. In the spinal cat spontaneous release of ir-NPY was detected in the mid-dorsal horn and this was unaltered by peripheral noxious thermal or noxious mechanical stimuli. As in the rat, release from intrinsic spinal neurones is most probable. The extensive spontaneous release of ir-NPY in both species suggests a widespread role in spinal cord function.

Bilaterally enhanced dorsal horn postsynaptic currents in a rat model of peripheral mononeuropathy.

Surface compound potentials were recorded from the surgically exposed lumbar spinal cord in anaesthetized rats which had had one sciatic nerve loosely ligatured 12-15 days previously, resulting in unilateral allodynia and hyperalgesia, as assessed behaviourally. These cord dorsum potentials were recorded in response to electrical stimulation of the ligatured and non-ligatured sciatic nerve, respectively, on both the ipsi- and contralateral side with respect to the stimulated nerve. Compared to potentials produced by stimulation of the non-ligatured sciatic nerve, electrical stimulation of large diameter fibres proximal to the ligatures resulted in a smaller afferent fibre input arriving at the spinal cord. However, larger net postsynaptic currents in the contralateral dorsal horn and a larger net postsynaptic current per unit of afferent fibre input were found in the ipsilateral and contralateral spinal cord. Such changes may result from structural changes or increased synaptic efficacy in the dorsal horn following peripheral nerve injury.

Afferent volley patterns and the spinal release of immunoreactive substance P in the dorsal horn of the anaesthetized spinal cat.

Microprobes bearing immobilized antibodies to the C-terminus of substance P were used to measure release of this neuropeptide in the spinal cord of the anaesthetized spinal cat in response to peripheral nerve stimulation. Release of substance P was just detectable in laminae I, II with 150 stimuli (0.5 Hz, 5 min) and was near maximal with 300 stimuli. Using two periods of stimulation of 10 min separated by 15 min, greater levels of substance P were detected during the second period. Fifteen to 25 min after two periods of peripheral nerve stimulation levels of substance P detected by microprobes were still elevated above those present prior to stimulation. Stimulation with bursts of three impulses when delivering a fixed number of stimuli resulted in detection of increased levels of substance P at sites adjacent to the areas of maximal release. The results suggest that maximal release of substance P from the central terminals of primary afferent fibres occurs with relatively few impulses and at low frequencies in agreement with what is known of release from the peripheral terminals of these fibres.

Placentoid bullous lesion of the lung.

Four adult patients presented with unilateral multicystic lung disease. The cysts had been detected years previously on chest radiographs in three patients. Two patients had histories of repeated childhood pneumonias. Preoperative diagnosis of bullous emphysema with rupture was made in three patients who presented with pneumothorax. Lobectomy was done in two patients and pneumonectomy in two patients. Macroscopically, each lung was spongy with cysts that contained gelatinous vesicular or grape-like structures resembling normal or molar placental tissue. Bullous emphysema was evident in one lung and marked panacinar emphysema in another. In one patient who had a lobectomy, the ipsilateral lobe of compressed lung re-expanded after surgery and proved to be cystic as well on subsequent radiographs. The vesicular and grape-like structures histopathologically are papillary structures with central edematous cores and a covering of cuboidal epithelial cells. Degenerate villi became either hydatidiform, fibrotic, or calcified. At low magnification the histology was similar to that of placenta with hydatidiform change. Emphysematous lung in which villiform structures appeared at the edges of bullae was found histologically in two patients. Lymphangiectasia was present in all patients. The placentoid bullous lesion has distinct macroscopic and microscopic features and is clinically unusual in that the cysts are unilateral and appear in otherwise healthy young adults. We do not know whether the lesion is a malformation or a peculiar devolution of localized bullous emphysema. We favor the latter interpretation. Torsion of lung may cause the lymphangiectasia and contribute to the unusual histology. Excision is curative.

Catheter complications associated with intraperitoneal chemotherapy.

Intraperitoneal administration of chemotherapy in ovarian carcinoma is currently under investigation. Numerous recent publications have described clinical studies employing a variety of chemotherapeutic drugs. Little information exists regarding the delivery systems employed or the complications encountered. This study reviews our experience with "single-use" and "long-term" catheters. Thirty-three catheters were placed in 28 patients. Of these catheters, 12 were long-term Tenckhoff catheters and 21 were temporary single-use catheters. Both types of catheters had complications associated with their usage. However, there was a dramatic difference in the number and severity of complications when the two groups were compared. Sixty-seven percent of the Tenckhoff catheters were associated with complications. Nineteen percent of the patients with single-use catheters experienced complications. This 19%, however, represented only 3.8% of the total number of single-use catheter insertions. In our hands, the temporary percutaneous approach has been a safe one, which is technically easy to perform with minimal complications.