Changes in immune function following surgery for esophageal carcinoma.

Changes in immune function due to surgical injury have been well-documented. Immunosuppression is one of the causes of infectious complications leading to organ dysfunction in critical illness. It is not known what kind of surgery in the daily clinical practice causes immunosuppression. Stress response and immune function following surgery for esophageal carcinoma, assuming a highly-stressed operation, were studied and then compared with the stress response and immune function following gastric surgery, a moderately-stressed procedure. Forty patients who underwent esophagectomy and 39 patients receiving gastric operation were studied. The concentrations of serum interleukin-6 (IL-6) were measured preoperatively, at 1, 2, and 6 h, and at 1, 3, and 10 d after operation. Total protein, serum albumin, rapid turnover protein, serum CRP, and cortisol were measured before operation and at 1, 3, 7, and 21 d after operation. ConA- and PHA-stimulated lymphocyte proliferation, IgA, IgG, and IgM were also measured preoperatively, and on 7 and 21 d following surgery. The patients were fed exclusively by total parenteral nutrition (TPN). A striking rise of IL-6 was observed, with a peak in both groups at 1 to 6 h following operation. The peak values were 419+/-30 pg/mL, which was approximately twice as high in the esophagectomy patients as in the gastrectomy patients (195+/-40 pg/mL). CRP and cortisol also increased after operation, and these increases were also significantly greater in the esophagectomy patients. ConA- and PHA-stimulated lymphocyte proliferation decreased significantly 7 d after esophagectomy (P<0.05), but was unchanged in the patients receiving gastrectomy. Suppression of cellular immunity correlated significantly with serum cortisol, and was preceded by a rise in serum IL-6. The IgA, IgG, and IgM levels, however, remained unchanged from their preoperative values throughout the study in both groups. Nutritional status in terms of serum protein, albumin, and rapid turnover protein, decreased postoperatively, but there was no difference between the two groups. It is, therefore, concluded that cell-mediated immunosuppression, preceded by a hyperinflammatory response, is an observable reaction in patients following esophageal surgery, but not in patients undergoing gastric surgery.     

Control of the dispersing process and pharmacokinetics in rats for lipid A analogue, E5531.

E5531 is a synthetic disaccharide analogue of lipid A which has a low toxicity but retains the ability to reduce production of tumour necrosis factor. This analogue has potential for use in the treatment of septic shock. An injectable formulation of E5531 would be useful, but dispersion in aqueous solution is a problem. In the present study the dispersing process for E5531 was evaluated using the pH-jump method (pH 11.0-->7.3). The size of the aggregates was decreased (reaching 20 nm) with increasing dispersing time in 0.003 M NaOH (pH 11.0). The membrane fluidity of the aggregates increased with increasing dispersing time. When prepared by the normal dilution method (pH 7.3-->7.3), the size of the aggregates remained constant at 140 nm and the membrane fluidity was smaller than that of samples prepared by the pH-jump method. This indicates that during dispersing at basic pH, the hydration proceeded in a normal manner, but then stopped, just after adjustment of the pH to 7.3. This suggests that the degree of hydration of the membrane is dependent on the dispersing time at pH 11.0. Using samples with different degrees of hydration and different membrane fluidity prepared by the pH-jump method, the pharmacokinetics and stability of the aggregates were evaluated after intravenous injection into rats. The data thus obtained confirmed that the membrane fluidity was correlated with the pharmacokinetics and stability in rat plasma. It was concluded that the pharmacokinetics of E5531 in rats can be controlled by changing the degree of hydration and membrane fluidity by means of using different dispersing times in alkaline solution (pH 11.0).     

Histochemical and ultrastructural observations on brown degeneration of human intervertebral disc

Thirty-eight fresh human intervertebral discs collected during anterior interbody fusion surgery were histochemically and ultrastructurally analyzed for pigments. Macroscopically, five stages of degeneration were classified according to the color, fibrosis, and fragility of the nucleus pulposus of the discs. In order to demonstrate lipofuscin granules, specimens were subjected to special staining procedures, including carbol fuchsin lipofuscin stain, the Schmorl's reaction, and autofluorescence. Lipofuscin granules were distributed from the inner layer of the annulus fibrosus to the nucleus pulposus. Such granules were numerous in cases of slight or severe degeneration, whereas fewer granules were found in cases of moderate degeneration. However, the stage of macroscopic degeneration of the intervertebral disc did not necessarily correlate with the incidence of lipofuscin granules. By ultrastructural observation, the morphological features of the components of the intervertebral disc and the ultrastructure of the lipofuscin granule were clarified. The ultrastructure of the "brown degeneration" disc exhibited markedly increased amorphous electron-dense bodies located among collagen fibrils in the matrix.     

Characterization of rat hyperplastic bile ductular epithelial cells in culture andin vivo

A novel intrahepatic biliary cell culture/in vivo transplantation system has been developed with an essentially pure population of bile ductular epithelial cells isolated from rat liver 6–12 weeks after bile duct ligation. In primary culture, these cells retain staining strongly for -glutamyltranspeptidase and glutathione S-transferase P. The cytoplasm of cultured bile ductular cells reacts with an anti-laminin antibody, but loses immunoreactivity with a monoclonal anti-cytokeratin 19 antibody. Semiconservative DNA synthesis in the cultured cells was dependent upon the continued presence of 10% fetal calf serum in the medium. Replicating bile ductular cells could be subcultured for a finite number of passages. In addition, freshly isolated bile ductular epithelial cells gave rise to well differentiated bile ductular structures when transplanted into the interscapular fat pads of syngeneic recipient rats.Presented at the Proceedings of the International Meeting on Normal and Neoplastic Growth in Hepatology, Bari, Italy, June 1989.This work was supported by USPHS Grant RO1 CA39225 to Dr. Sirica by the National Cancer Institute, Department of Health and Human Services.     

An unusual case of rhythmic movement disorder

Rhythmic movement disorder is one of the sleep-wake transition disorders listed in the International Classification of Sleep Disorders. According to this classification, the condition commonly occurs in infants and toddlers, and persistence beyond 4 years of age is unusual. Recently, we encountered a case in which rhythmic movement disorder persisted up until the age of 12 years with spikes registering on the sleep electroencephalogram. Epileptic seizure was ruled out because of the characteristic rolling movement, absence of any other epileptic symptoms (e.g. vocalization and tonic-clonic seizure) and cessation as a result of removal of the blanket.     

Effect of 3 mg melatonin on jet lag syndrome in an 8-h eastward flight

In order to assess the effect of melatonin on jet lag a field study was undertaken. The process of re-entrainment of circadian melatonin rhythm was investigated in six subjects. Except during 24-h blood sampling, the subjects were exposed to natural zeitgeber (time giver) outdoors and given 3 mg melatonin at 23:00 h. The subjects were exposed to bright sunlight from 3000 to 12000 lx. All of them showed orthodromic re-entrainment with taking melatonin, while two out of the six did not show orthodromic re-entrainment without taking melatonin. Melatonin accelerated the rate of the re-entrainment of the circadian melatonin rhythm. Melatonin was useful to jet travel from Tokyo to Los Angeles.     

Radiation-induced diffuse brain injury in the neonatal rat model--radiation-induced apoptosis of oligodendrocytes

The mechanism of radiation-induced diffuse brain injury was investigated using a model of delayed myelination in the irradiated neonatal rat brain in which the number of oligodendrocytes decreases without associated necrosis of the cerebral white matter. Immunohistochemical analysis using antibody against the large myelin-associated glycoprotein, a specific marker of oligodendrocytes at an early stage of development, showed that the number of the oligodendrocytes associated with myelination decreased in the irradiated hemisphere 1 day after irradiation and remained low until 5 days after irradiation. In situ terminal deoxynucleotidyl transferase-mediated nick end-labeling assay revealed that apoptosis mainly occurred in the cerebral white matter of the irradiated hemisphere. Three hours after irradiation, apoptotic cells were found in the subcortical white matter and the periventricular white matter. Six hours after irradiation, apoptotic cells were found in the internal capsule, and the numbers of apoptotic cells in the periventricular white matter and subcortical white matter increased. One day after irradiation, the number of apoptotic cells in the periventricular white matter decreased. Three days after irradiation, apoptotic cells were not observed in the cerebral white matter. These results suggest that the oligodendrocytes associated with myelination may be damaged via radiation-induced apoptosis, and depletion of the oligodendrocytes may cause delay of myelination.     

Early reactions after reimplantation of the tendon of supraspinatus into bone. A study in rabbits

In 14 rabbits we determined the origin of the cells effecting healing of the tendon of supraspinatus inserted into a bony trough. After two weeks both the cellularity of the underlying bone and the thickness of the subacromial bursa were significantly increased in the operated compared with the control shoulders. The cellularity of the stump of the tendon, however, was significantly decreased in the operated shoulders. In this model, both the underlying bone and the subacromial bursa but not the stump of the tendon contributed to the process of repair. We conclude that the medial stump should be debrided judiciously but that cutting back to bleeding tissue is not necessary during repair of the rotator cuff. Moreover, great care should be taken to preserve the subacromial bursa since it seems to play an important role in the healing process.