Does the pineal gland play a role in neuroendocrine fear responses?

The pineal gland secretes melatonin under an influence of suprachiasmatic nucleus neurones. Pinealectomy or melatonin administration affects behavioural responses to novel stimuli. Fear or novel stimuli inhibit vasopressin (VP) and facilitate oxytocin (OT) or prolactin (PRL) release from the pituitary. Thus the suprachiasmatic nucleus-pineal gland system may modulate VP, OT and PRL responses to conditioned fear stimuli. In the present experiments with male rats, pinealectomy or melatonin administration did not significantly change VP, OT or PRL responses to conditioned fear stimuli. Electrolytic lesions of the suprachiasmatic nuclei impaired VP but not OT or PRL responses. The results show that the pineal gland is not involved in neuroendocrine responses to conditioned fear stimuli and suggest that the suprachiasmatic nucleus is necessary for the VP response to fear stimuli.     

Efficacy of the axially loaded pivot shift test for the diagnosis of a meniscal tear

Although magnetic resonance imaging (MRI) has improved the diagnostic accuracy of meniscal pathology, the authors believe that physical examination remains essential to the evaluation of knee pathology. In this study, the diagnostic accuracy of five clinical tests for meniscal pathology was prospectively evaluated in 160 patients, who thereafter underwent arthroscopy. 69% (109 knees) of the knees tested had associated ACL deficiency. There were 144 meniscal lesions in 130 of the 160 knees which were examined. The sensitivity of the tests was lower than the specificity. Conventional tests such as McMurray and Apley tests showed a low accuracy rate of 45% and 28% respectively. The diagnostic value of the axially loaded pivot shift test was significantly higher, indicating that this remains a useful diagnostic aid.     

Effects of N-ethylmaleimide on the structure of skinned frog skeletal muscles

Summary The effects of N-ethylmaleimide (NEM) and other sulfhydryl modifiers on the structure of skinned frog skeletal muscles were studied using the X-ray diffraction technique. In sartorius muscle with full overlap between the thick and thin filaments, 0.1-1.0 mM NEM changed the intensity ratio of the (1,0) and (1,1) equatorial reflections from 4.35 to 0.72, and the (1,0) spacing of the hexagonal filament lattice from 40.4 to 41.4 nm. The axial X-ray diffraction pattern showed weak myosin layer-lines after the NEM treatment but enhancement of the actin layer-lines was not observed. In overstretched semitendinosus muscle, NEM did not affect the equatorial spacing but the myosin layer-lines were weakened. These results indicate that modification of myosin by NEM destroys the helical arrangement of myosin heads around the shaft of the thick filament and that when thin filaments are available, myosin heads move towards, and possibly bind to them. This binding is different from that in rigor since the ladder-like appearance of the higher actin layer-lines, which is typical of patterns from rigor muscles, was not observed. On removal of ATP after the NEM treatment, the diffraction pattern showed features characteristic of that from normal rigor muscles but no tension was produced. The pattern showed well-defined samplings on layer-lines in the small-angle region, indicating the presence of an extensive lattice order and exact axial alignment of the filaments. The first actin layer-line did not show samplings from the superlattice of the thick filaments, which are observed on the myosin layer-lines in patterns from resting muscles. This indicates that in NEM-treated rigor muscles the pattern of binding of myosin heads to the thin filaments is not influenced by the azimuthal orientation of the thick filament.     

Expression of Adhesion Molecules and Cytokines on Saphenous Veins in Chronic Venous Insufficiency

The objective of this study was to assess the relationship of signaling molecules to monocyte/ macrophages as a precursor to venous valve and venous wall dysfunction in patients with varicose veins. One of the hallmarks of venous dysfunction is destruction of venous valves with subsequent reflux and elevation of distal venous pressure. We recently observed that monocytes/macrophages migrate into the venous walls and valves of patients with venous insufficiency. There, they may play a role in the pathogenesis of primary venous insufficiency. If so, an important element in their performance would be the interaction between the monocytes and the endothelium as a precursor of damage to venous valves and the venous wall. To explore this interaction, immunohistochemistry was carried out to detect adhesion molecules and cytokines in surgical specimens removed during surgical therapy. Twenty-four surgical specimens consisting of proximal saphenous vein and subterminal valve were obtained using minimally traumatic technique in 6 males and 18 females who ranged in age from 31 to 79 years. Reflux was confirmed preoperatively by duplex technique, and severity was classified by the CEAP classification of the American Venous Forum. Ten patient limbs were class 2, eight were class 3, four were class 4, and two were class 6. The venous specimens were labeled using monoclonal antibody against ICAM-1, E-selectin, IL-1alpha, and TNF-alpha. CD68 was used for detection of monocytes/macrophages. Our results indicate that not only luminal venous endothelium but also endothelium in the vasa vasora of refluxing saphenous veins is activated, as indicated by the up-regulation of ICAM-1. However, IL-1alpha and TNF-alpha were increased in only selected specimens and are mainly detected in the vein wall. The factors that serve as trigger mechanisms to activate cells in the pathogenesis of primary venous dysfunction remain to be explored.     

Prognostic significance of loss of heterozygosity on chromosome 9p21–22 in human esophageal cancer

Background Deletions involving chromosome 9p21, on which the tumor suppressor genep16/MTS1 is located, have been noted in esophageal cancer. We investigated the relationship between the deletion of chromosome 9p21–22 and the clinical features of esophageal cancer. Methods We examined the loss of heterozygosity (LOH) on chromosome 9p21–22 in 56 esophageal cancers using polymerase chain reaction (PCR) analysis and 2 microsatellite markers (RPS6 and IFNA). Results In 18 out of 50 informative cases (36%), LOH had occurred at 1 or 2 loci on chromosome 9p21–22. We found no relationship between LOH on chromosome 9p21–22 and patient sex, age tumor length, location, histologic differentiation, depth of tumor invasion, the extent of lymph node metastasis, histologic stage, or curability. Among 35 patients without an absolute noncurative resection, the mean survival of 11 patients with LOH on chromosome 9p21–22 was 19.3 months, compared with 42.3 months for 24 patients with a normal allele; thus, the survival rate of those with LOH was significantly lower than that of patients without LOH on chromosome 9p21–22 (log-rank test;P=0.03). Conclusion These data suggest that LOH on chromosome 9p21–22, on which the cell-cycle regulatorp16/MTS1 gene is located, may be related to cancer development, and probably can serve as a clinical marker for evaluating a patient's prognosis.     

Pyloric motor abnormality in patients with infantile hypertrophic pyloric stenosis

There are no published data of manometric studies of pyloric motor function in patients with infantile hypertropic pyloric stenosis (IHPS). The present study attempted to examine the characteristics of motor abnormality of the pylorus in five children with IHPS. Using a transducer-built-in manometric catheter cannulated through the pylorus under fluoroscopy, the pressure in the pyloric canal was recorded continuously over 3 h during fasting. Clusters of high-amplitude spastic contractions of over 300 mmHg were recorded at intervals. The frequency was 1–3/min (mean 1.7 cpm) and the duration was 7–15 s. These periodic spastic contractions were suppressed temporarily for 20–30 min after intravenous injection of 0.01 mg/kg atropine. After pyloromyotomy, these spastic contractions decreased remarkably in amplitude, but there were no changes in frequency. It is concluded that the underlying motor abnormality observed in hypertrophied pyloric muscle is clusters of high-amplitude contractions, although more precise measurements of basal pyloric pressure are needed to explore the pathophysiology of IHPS in detail. The effect of pyloromyotomy may be related to the decrease in high-amplitude contractions. Accepted: 26 May 1998     

Longer-term diabetic patients have a more frequent incidence of nosocomial infections after elective gastrectomy

Diabetes mellitus (DM) is one of the risk factors for the development of postoperative nosocomial infections in surgical patients. We conducted this retrospective study to elucidate the perioperative risk factors for postoperative nosocomial infections in diabetic patients undergoing elective gastrectomy. Chart review was performed on diabetic and nondiabetic patients undergoing elective gastrectomy for gastric malignancy from January 1992 through April 1999. Fourteen of the 83 diabetic patients, and 23 of the 284 nondiabetic patients developed postoperative nosocomial infections. Statistical comparisons of multiple variables were made between patients with and without postoperative nosocomial infections. In diabetic patients, univariate analysis showed that longer-term DM (especially longer than 10 yr) was associated with a significantly increased risk for postoperative nosocomial infections. Multiple logistic regression analysis showed that DM lasting longer than 10 yr was an independent risk factor for postoperative nosocomial infections (odds ratio, 6.8; 95% confidence interval, 1.7 to 27.1). In nondiabetic patients, similar analysis showed that age was an independent risk factor for postoperative nosocomial infections. We conclude that patients with longer-term DM had a significantly greater incidence of postoperative nosocomial infections after elective gastrectomy. Implications: Postoperative nosocomial infection is one of the major problems in diabetic patients. This study demonstrated that postoperative nosocomial infections were more common in patients undergoing elective gastrectomy if they had diabetes mellitus longer than 10 yr.