Further studies on interactions between periaqueductal gray, nucleus accumbens and habenula in antinociception.

Previous findings from this laboratory with the intracerebral microinjection technique suggested that the periaqueductal gray (PAG), nucleus accumbens, and habenula might constitute a unidirectional loop to play their roles in pain modulation. In the present study we demonstrate that intra-habenular injection of naloxone antagonizes the analgesia elicited by morphine injected into the periaqueductal gray (PAG) and that intra-accumbens injection of naloxone is capable of attenuating the analgesic effects of morphine injected into the habenula. These results indicate that the relationships between these nuclei may be more complex than the putative unidirectional loop.     

Research on the relation between intrauterine infection and intrauterine growth retardation]

To investigate the relationship between intrauterine infection and IUGR, the following studies have been carried out: (1) measurement of specific antibodies of Toxoplasma (Toxo) and Cytomegalovirus (CMV) in the umbilical serum samples from 30 cases of IUGR with 26 normal newborn infants as controls; (2) follow-up exam on 14 positive cases in 17-25 months. The results showed that in 30 IUGR cases 14 were found to have Toxo and CMV infection, with an incidence significantly higher than that in the control group. One third of the infected patients were found to have retarded growth afterbirth and 63.63% of them appeared to have an increase in BAEP. This suggested that regular follow-up is indicated in these cases.     

超声引导下肿瘤内注射^90钇玻璃微球的肝癌综合治疗

超声引导下对２８例肝癌病人进行了肿瘤内注射＾９０钇玻璃微球（Ｙ－９０ＧＴ ＭＳ）为主的综合性治疗（部分病人配合肿块周边注射无水酒精及门静脉穿刺化疗）。随访２～１６个月（平均７．９个月），病人全健在。肿瘤缩小率为９１％，其中显著缩小达７５％；肿块回声呈致密增强，少数呈混合型或等回声型；肿瘤内及周边血流信号显著减少；原甲胎蛋白升高者１３例，１１例显著下降，其中６例降至正常；病人症状减轻，全身情况改善。     

THE EFFECT OF ACUPUNCTURE ON PREVENTION AND TREATMENT OF ISCHEMIC ARRHYTHMIA AND THE RELATION BETWEEN EFFECT OF ACUPUNCTURE AND CHOLINERGIC MUSCARINE-LIKE RECEPTORS

For investigating the effect of acupuncture on ischemic arrhythmia and its mech-anism, adult albino rats with ligated anterior descending branch of coronary artery as experimentalmodel were treated with or without acupuncture, and others with imitative operation but without bothcoronary artery ligation and acupuncture treatment were used as control. It was found in acupuncturegroup that the fibrillation-liability of ischemic myocardium was efficiently decreased, the affinity ofAch-M receptors on membranes of ischemic myocardium was markedly increased, and the tolerance ofischemic myocardium to atropine was elevated in the experiment of atropine inducing fibrillation.These results indicate that acupuncture may play a therapeutic role on ischemic arrhythmia throughactivating the activity of muscarine-like receptors of cholinergic nervous system.     

Fluorescence in situ hybridization analysis of chromosome 12p in paraffin-embedded tissue is useful for establishing germ cell origin of metastatic tumors.

The over-representation of chromosome 12p sequences is crucial for the development of invasive testicular germ cell tumors. Testicular cancer patients may have metastatic tumors of diverse histologic types, including adenocarcinoma, undifferentiated carcinoma, sarcoma, or other malignancies that lack features of germ cell tumors. We sought to investigate the possible germ cell origin of such tumors using interphase fluorescence in situ hybridization. In all, 10 metastatic malignant somatic-type tumors from patients with histories of testicular cancer, as well as one malignant somatic-type tumor from a patient with primary mediastinal germ cell tumor were studied and included: adenocarcinoma (five cases), poorly differentiated carcinoma (one), sarcoma (four), and neuroendocrine carcinoma (one). The tumors were analyzed using fluorescence in situ hybridization using 12p spectrum green and 12 centromeric spectrum orange probes in paraffin sections. The patients ranged in age from 27 to 55 years (mean, 43). Colon and lung cancers from patients without germ cell tumors were used as controls. Adequate signals were observed in all tumors. Gain of chromosome 12p was seen in six tumors. None of the control tumors showed 12p amplification. Fluorescence in situ hybridization for 12p amplification in routinely processed surgical specimens is a useful adjuvant diagnostic tool in confirming the germ cell origin of metastatic tumors having the histologic appearance of somatic-type neoplasms.     

Septal-lateral annnular cinching perturbs basal left ventricular transmural strains.

OBJECTIVE: Septal-lateral annular cinching ('SLAC') corrects both acute and chronic ischemic mitral regurgitation in animal experiments, which has led to the development of therapeutic surgical and interventional strategies incorporating this concept (e.g., Edwards GeoForm ring, Myocor Coapsys, Ample Medical PS3). Changes in left ventricular (LV) transmural cardiac and fiber-sheet strains after SLAC, however, remain unknown. METHODS: Eight normal sheep hearts had two triads of transmural radiopaque bead columns inserted adjacent to (anterobasal) and remote from (midlateral equatorial) the mitral annulus. Under acute, open chest conditions, 4D bead coordinates were obtained using videofluoroscopy before and after SLAC. Transmural systolic strains were calculated from bead displacements relative to local circumferential, longitudinal, and radial cardiac axes. Transmural cardiac strains were transformed into fiber-sheet coordinates (X(f), X(s), X(n)) oriented along the fiber (f), sheet (s), and sheet-normal (n) axes using fiber (alpha) and sheet (beta) angle measurements. Results: SLAC markedly reduced (approximately 60%) septal-lateral annular diameter at both end-diastole (ED) (2.5+/-0.3 to 1.0+/-0.3 cm, p=0.001) and end-systole (ES) (2.4+/-0.4 to 1.0+/-0.3 cm, p=0.001). In the LV wall remote from the mitral annulus, transmural systolic strains did not change. In the anterobasal region adjacent to the mitral annulus, ED wall thickness increased (p=0.01) and systolic wall thickening was less in the epicardial (0.28+/-0.12 vs 0.20+/-0.06, p=0.05) and midwall (0.36+/-0.24 vs 0.19+/-0.11, p=0.04) LV layers. This impaired wall thickening was due to decreased systolic sheet thickening (0.20+/-0.8 to 0.12+/-0.07, p=0.01) and sheet shear (-0.15+/-0.07 to -0.11+/-0.04, p=0.02) in the epicardium and sheet extension (0.21+/-0.11 to 0.10+/-0.04, p=0.03) in the midwall. Transmural systolic and remodeling strains in the lateral midwall (remote from the annulus) were unaffected. CONCLUSIONS: Although SLAC is an alluring concept to correct ischemic mitral regurgitation, these data suggest that extreme SLAC adversely effects systolic wall thickening adjacent to the mitral annulus by inhibiting systolic sheet thickening, sheet shear, and sheet extension. Such alterations in LV strains could result in unanticipated deleterious remodeling and warrant further investigation.     

The adverse effect of treatment prolongation in cervical cancer by high-dose-rate intracavitary brachytherapy.

BACKGROUND AND PURPOSE: The potential risk of prolongation of treatment time in cervical cancer has been reported for many low-dose rate (LDR) studies, with an estimated loss of local control ranging from 0.3 to 1.6% per day of treatment prolongation. Since the treatment schedule for fractionated high-dose rate intracavitary brachytherapy (HDRICB) is not directly comparable with that for low-dose rate studies, this report aims to evaluate the adverse effect of treatment prolongation specifically for cervical cancer treated with HDRICB. MATERIAL AND METHODS: From September 1992 to December 1997, 257 patients diagnosed with uterine cervical cancer (35 Ib, 26 IIa, 122 IIb, 10 IIIa, 57 IIIb, 7 IVa), who underwent external radiotherapy combined with between two and four courses of HDRICB and a minimum of 3 years of follow-up (median 57 months), were analyzed. Treatment consisted of irradiation of the whole pelvis with 44-45 Gy consisting of 22-25 fractions by 5 weeks, with the dose boosted to 54-58 Gy (with central shielding) for patients diagnosed as FIGO stage IIb-IVa bilateral parametrial disease. HDRICB was performed using an Ir-192 remote afterloading technique at 1-week intervals. The standard prescribed dose for each course of HDRICB was 7.2 Gy to point A for three insertions (before July 1995), or 6.0 Gy to point A for four insertions (after July 1995). Total prescribed point A doses (external beam radiotherapy+HDRICB) ranged from 58 to 71.6 Gy (median, 65.6 Gy) for stage IB-IIA, while analogous dosage for larger lesions (stage IIb-IVa) ranged from 59 to 75.6 Gy (median, 65.6 Gy). Kaplan-Meier and multivariate analyses were used to test the effect of treatment time on pelvic control rate (PCR) and cause-specific survival (CSS) at 5 years. RESULTS: Median treatment time was 63 days. For all stages of disease, the 5-year CSS and PCR were significantly different comparing treatment times of less than and greater than or equal to 63 days [83% and 65% (P=0.004], 93% and 83% (P=0.02), respectively]. These associations were also significant for stage Ib/IIa [97% and 79% (P=0.01), and 100% and 87% (P=0.02), respectively), but not for stage IIb [75% and 72% (P=0.79), and 93% and 87% (P=0.83), respectively] or stage III [66% and 49% (P=0.2), and 83% and 72% (P=0.21), respectively]. Multivariate analysis identified three prognostic factors for CSS, stage (P<0.001), tumor response to external RT (P=0.001), and overall treatment time (OTT; P=0.006). Prognostic factors for pelvic failure were stage (P<0.001), tumor response to external RT (P=0.001), and OTT (P=0.03). Prolongation of treatment time resulted in a daily decrease in pelvic control rate of 0.67% overall, and 0.43% for stage Ib-IIa, 0.57% for stage IIb, and 0.73% for stage III patients. CONCLUSION: Analysis of the data from the current study demonstrates that the adverse effect of treatment prolongation was observed later in the treatment course for the high-dose rate (HDR) series compared to the LDR analog, however, treatment-time prolongation still negatively influenced the cause-specific survival and pelvic control rate for both dosage groups.     

Neuroprotective effect of estrogen after chronic spinal cord injury in ovariectomized rats

BACKGROUND: At present, there is still lack of effective drugs for chronic spinal cord injury, whereas it is found recently that estrogen has a neuroprotective effect on brain and spinal cord injuries. OBJECTIVE: To observe the effect of estrogen on the apoptosis of nerve cells after gradual chronic spinal cord injury in ovariectomized rats. DESIGN: A randomized controlled animal trial. SETTING: Institute of Orthopaedics, the Second Hospital of Lanzhou University. MATERIALS: Sixty-five female Wistar rats of common degree, weighing 220–250 g, were provided by the experimental animal center of Lanzhou University. The rats were randomly divided into sham-operated group (n =5), estrogen-treated group (n =30) and saline control group (n =30), and the latter two groups were observed at 1, 3, 7, 14, 28 and 60 days respectively, and 5 rats for each time point. METHODS: All the rats were treated with bilateral oophorectomy 2 weeks before the experiment. T10 vertebral lamina was revolved into using plastic screw. The spinal canal impingement was not induced initially. After that, the original incision was opened to expose the screw every 7–10 days. MAIN OUTCOME MEASURES: The apoptosis and Caspase-3 positive cells in the damaged spinal cord were detected using terminal deoxynucleotidal transferase-mediated dUTP-biotin nick end labeling (TUNEL) method and Caspase-3 immunohistochemical staining at 1, 3, 7, 14, 28 and 60 days after chronic spinal cord injury respectively. RESULTS: Totally 65 rats were used, and the deleted ones during the experiment were supplemented by others. Changes of Caspase-3 expression after spinal cord injury: In the sham-operated group, only a small amount of Caspase-3 proteins were observed in the rat spinal cord, mainly located in motor neurons of spinal cord anterior horn. In the estrogen-treated group and saline control group, positive cells expressed occasionally at 1 day postoperatively, began to increase obviously at 7 days after injury, strongly expressed at 14 and 28 days, but decreased at 60 days, mainly located in the neurons of spinal cord gray matter anterior horn, and they expressed fewer in the motor neurons and white matter of ventral horn, and there were obvious differences between the estrogen-treated group and saline control group at 7, 14, 28 and 60 days (P < 0.05). CONCLUSION: Estrogen can reduce the apoptosis of nerve cells and promote the recovery of neurological function following gradual chronic spinal cord injury.     

Expression of neuron-specific enolase and olfactory marker protein in the developing olfactory mucosa of human fetuses]

OBJECTIVE: To study the expression of neuron-specific enolase (NSE) and olfactory marker protein (OMP) in the developing olfactory mucosa of human fetuses. METHOD: The expression of NSE and OMP in the olfactory mucosa of 6 human fetuses (12, 16, 20, 24, 28 and 34 weeks) was studied using the technique of immunohistochemistry. RESULTS: NSE immunological positive reactions were seen in all 6 fetal mucosa from gestational 12 (G12) to G34, with plenty of positive-stained dual-pole neuron cells. At G12, the positive cells aligned tightly, the cell bodies were localized in the lower portion of olfactory epithelium and the positive-stained area occupied upper 2/3 of fetal nasal mucosa. With the development, the positive cells gradually became multilayer, but the density and the relative area of positive-cells reduced. At G34, the positive cells were located only in upper 1/3 of nasal mucosa. OMP-positive reactions were localized in a few dual-pole neurons at G12, the number was much less than NSE-positive cells in the same fetus. With the development, the OMP-positive cells gradually increased with most of the cell bodies located in the upper portion of epithelium, but number still relatively less than the NSE-positive cells at the same age. CONCLUSION: At G12, there were lots of olfactory neuron in the olfactory mucosa and only a few olfactory neurons had became mature. With the development, the olfactory epithelial area reduced but the number of mature olfactory neurons increased. At the last trimester, fetal olfactory sensor was almost matured.     

Long-term application of diethylstilbestrol upregulates expressions of μ- and m-calpains in pituitary intermediate lobe of female Wistar rats

BACKGROUND: During formation of prolactin neoplasia, how cells and its structure in adenohypophysis affect prolactin cells should be further studied. Intermediate lobe can be regarded as a driving region to release prolactin (PRL) and may promote formation of prolactin neoplasia in pituitary anterior lobe. OBJECTIVE: To observe the effect of diethylstilbestrol (DES) on the expressions of μ and m-calpains in pituitary intermediate lobe of female Wistar rats. DESIGN: Observational contrast animal study. SETTING: Beijing Neurosurgical Institute. MATERIALS: A total of 21 female Wistar rats, 3 weeks old weighing 70–80 g were housed with free access to tap water and standard pellet food. They were kept in a CL-grade condition, at (24±1)℃ and a humidity of (55±5)%, and with a 12 hours day-night cycle. Caprine anti-μ- and m-calpains antibodies were provided by Santa Cruz Biotechnology, CA, USA; rabbit-anti-PRL antibodies by Dako, Denmark; rabbit-anti-ACTH antibody by Boster Company, Wuhan. METHODS: The experiment was carried out in Pathophysiological Department and Animal Laboratory, Beijing Neurosurgical Institute from August 2006 to January 2007. ① Rats were randomly divided into groups with 7 in each group, including vehicle control group, in which rats were injected intraperitoneally with sun-flower seed oil (1 mL/kg, twice a week) for 16 weeks; DES group, where animals were administered with DES (5 mg/kg, twice a week) for 16 weeks; DES + vehicle control group, in which DES was administered for 12 weeks at the same dose with those in DES group, and then was discontinued and replaced by sun-flower seed oil (1 mL/kg, twice a week) for the following 4 weeks. ② At 16 weeks later, pituitary tissue was dealt with HE staining and PRL immunohistochemical examination to observe evoke of tumor; meanwhile, immunohistochemical examination was used to observe expression of PRL of pituitary anterior lobe, expressions of μ- and m-calpains of pituitary intermediate lobe and distribution of adrenocorticotropin. MAIN OUTCOME MEASURES: ① Expression of PRL of pituitary anterior lobe, expressions of μ- and m-calpains of pituitary intermediate lobe and distribution of adrenocorticotropin. ② Morphological observation of pituitary tissue. RESULTS: All 21 rats were involved in the final analysis. ① Results of immunohistochemical examination: Morphological changes of neoplasia in DES group were strongly positive to PRL, and this suggested that formation of prolactin adenoma was observed in pituitary tissue. As compared with vehicle control group, expression of adrenoeorticotropic hormone (ACTH) was increased in both DES group and DES + vehicle control group. In addition, expressions of μ- and m-calpains in pituitary intermediate lobe were higher in DES group than that in vehicle control group. Otherwise, expressions of m-calpains in pituitary intermediate lobe was decreased in DES + vehicle control group, but expression of μ-calpains was still increased. ② Morphological observation of pituitary tissue: Gland tubes were orderly arranged in rats in vehicle control group. Anterior pituitary gland in rats of DES group demonstrated an apparent disappearance of gland tubes and a relatively large-scaled vasculature formation, namely the vascular lake lined by tightly arranged endothelial cells. Local integrated tumor cell arrangements were also detected. In addition, the border between the IL and the anterior lobe was locally blurred. The definite tumor-like changes in pituitary tissues were confirmed in 6 of 7 female Wistar rats in DES group, and one spontaneous occurrence of tumor formation was found in vehicle control group. In DES + vehicle control group, DES withdrawal led to the subtile emergence of gland tube cavity, although tumor-like cells still existed in 4 of 7 rats, suggesting occurrence of the tumor regression due to the withdrawal of DES. CONCLUSION: A long-term application of DES can enhance the expressions of ubiquitours neutral cysteine protease in pituitary intermediate lobe and this suggests that both of them play a key role in release of hormone and formation of prolactin neoplasia through directly promoting PRL expression and release of neighboring pituitary intermediate lobe.