Acute Immobilization Stress and Intraventricular Injection of CRF Suppress Naloxone-Induced LH Release in Ovariectomized Estrogen-Primed Rats

The present study was undertaken to evaluate the role and possible interaction of the endogenous opioid peptide (EOP) and corticotropin-releasing factor (CRF) in the acute stress-induced suppression of gonadotropin secretion in ovariectomized estrogen-primed rats. An intravenous (i.v.) injection of naloxone (10 or 20  mg/kg), an EOP antagonist, significantly elevated serum luteinizing hormone (LH) levels within 10  min in non-stressed animals. The naloxone-induced LH release was completely eliminated when tested 30  min after the onset of acute immobilization. In a subsequent study, it was found that suppression of the naloxone-induced LH release occurred as early as 5  min after the stress onset, and was still evident 60  min after the end of a 30-min period of immobilization. The effect of naloxone was restored 3  h after liberation of the animal from the 30-min immobilization. An intraventricular (i.c.v.) injection of CRF (1 or 5  μg) also significantly suppressed, in a dose-related manner, the effect of a subsequent i.v. injection of naloxone. However, an i.c.v. injection of α -helical CRF(9-41) (25 or 50  μg), a CRF antagonist, prior to immobilization, could not interfere with the suppressive effect of stress on naloxone-induced LH release. These results suggest that both acute immobilization stress and CRF can inhibit the LH secretory activity without mediation by EOP neurons. However, the stress-related suppression may involve non-CRF mechanism(s).     

The efficacy and safety of laparoscopic nephrectomy in patients with three or more comorbidities

OBJECTIVES: Laparoscopic surgery for kidney treatment is a common procedure. However, the efficacy of this procedure in patients with several comorbidities has not been well investigated. We conducted a retrospective comparison of results of laparoscopic surgery between patients with several comorbidities and patients with no comorbidity to access the efficacy and safety of this procedure. METHODS: The subjects were 20 patients with three or more comorbidities (group A) and 46 patients with less than three comorbidities (group B). These 66 patients were 48 men and 18 women with a mean age of 62.3 years (age range, 24-83 years). The data from these two groups were compared for American Society of Anesthesiology (ASA) physical status score, previous surgical history, duration of surgery, estimated blood loss, tumor size, complications during and after surgery, conversion rates, time to oral intake, and length of hospital stay. RESULTS: The initial ASA score and age were significantly higher for the patients with comorbidities (P < 0.0001, P = 0.0008, respectively). All other variables before, during, and after surgery were similar for both laparoscopic groups. However, the incidence of atelectasis of laparoscopy was higher than that of open surgery. CONCLUSIONS: Laparoscopic nephrectomy for patients with comorbidities is safe and minimally invasive. Further investigation to prevent atelectasis is necessary.     

In vivo presynaptic and postsynaptic striatal dopamine functions in idiopathic normal pressure hydrocephalus.

Differentiation of impaired gait seen in idiopathic normal pressure hydrocephalus (iNPH) from parkinsonian gait is sometimes a great challenge and important for future medication in the clinical setting. To investigate dopaminergic contribution to its pathophysiology, two aspects of the trans-synaptic dopamine functions in the striatal region in eight iNPH patients na?ve to dopaminergic drugs were examined using positron emission tomography with a presynaptic marker [11C]CFT ([11C]2-beta-carbomethoxy-3beta-(4-fluorophenyl) tropane) that binds to dopamine transporter and a postsynaptic marker [11C]raclopride that binds to D2 receptor. Quantitative values of binding potentials (BPs) for [11C]CFT and [11C]raclopride were compared between patients and eight age-matched healthy subjects. The BPs and magnetic resonance imaging-based morphometric measures in iNPH were used for correlation analyses between the magnitude of binding of these in vivo markers and clinical severity of the patients. Analysis of variance showed significant reduction in [11C]raclopride binding in the putamen and nucleus accumbens (P<0.05, corrected for multiple comparison) and unchanged striatal [11C]CFT binding in iNPH. The dorsal putamen [11C]raclopride binding correlated negatively with gait severity (r=0.720, P<0.05), and the nucleus accumbens [11C]raclopride binding correlated positively with emotional recognition score (r=0.727, P<0.05) in the disease group. No significant relationship was observed between BPs and morphometric measures. The current result of the postsynaptic D2 receptor reduction along with preserved presynaptic activity in the nigrostriatal dopaminergic system reflects a pathophysiology of iNPH. Postsynaptic D2 receptor hypoactivity in the dorsal putamen may predict the severity of gait impairment in iNPH.     

Prognosis for patients with carcinoma in the middle third of the stomach

In 268 of the 1,115 patients (24.0%) with gastric cancer who underwent a curative resection in our clinics, the tumor was located in the middle third of the stomach. The clinicopathological features and prognosis of these patients were divided into two groups, according to site of the tumor: anterior wall (n = 58) vs. other sites (n = 210). Clinicopathological factors did not differ between the two groups. The survival time for patients with a tumor in the anterior group was shorter than that for patients with a tumor in other areas (P < 0.05). The five-year survival rate was 79.3% for patients with an anterior tumor and 91.9% for those with a tumor at a different site. A multivariate analysis indicated lymph node metastasis, serosal invasion, and anterior wall location to be independent prognostic factors indicative of a poor prognosis when the tumor was located in the middle third of the stomach. For such patients, close follow-up is needed to detect possible recurrences. © 1993 Wiley-Liss, Inc.     

Effect of intermittent parathyroid hormone (1-34) treatment on the bone response after placement of titanium implants into the tibia of ovariectomized rats.

PURPOSE: This study investigated the effect of parathyroid hormone (1-34) [PTH(1-34)] on bone reactions after tibial placement of titanium screw implants into ovariectomized rats. MATERIALS AND METHODS: Twelve-week-old female Wistar rats were divided into 3 groups of 24. The first group (Sham group) was sham-operated; the second group (OVX group) was ovariectomized only; and the third group (PTH group) was subcutaneously administered 30 microg/kg PTH in the dorsal region 3 days per week starting the fourth week after ovariectomy until the end of the experiment. Titanium screw implants were placed in the proximal metaphysis of the tibia of all 3 groups at 168 days after surgery. The animals were killed 7, 14, 28, and 56 days after implantation. Undecalcified sections were prepared and evaluated by light microscopy. Histomorphometric measurements were obtained using a computer-based image analyzer to quantify the unit bone mass around the implant and the rate of implant-bone contact. RESULTS: When PTH administration was started 21 days after ovariectomy, the volume density of bone around implants in the PTH group was almost the same as that of the Sham group throughout the entire observation period. This finding suggests that not only can intermittent human PTH(1-34) administration prevent resorption of newly generated trabeculae around an implant but also it can aid in the recovery of bone volume lost due to ovariectomy. CONCLUSION: When dental implants are applied to jaw bone showing trabecular bone loss, it may be possible to increase bone density around an implant by intermittent human PTH(1-34) administration and thereby improve clinical results.     

CCR1 acts downstream of NFAT2 in osteoclastogenesis and enhances cell migration.

We found that a chemokine receptor gene, CCR1, acts downstream of NFAT2 in RANKL-stimulated RAW264 and bone marrow cells. The upstream regulatory region of CCR1 showed RANKL-dependent and CsA-suppressible promoter activity. Downregulation of the expression and function of CCR1 suppressed cell migration. INTRODUCTION: We previously reported that the expression of NFAT2 induced by RANKL is a key process for progression to multinucleated cells in an in vitro osteoclastogenesis system. Identifying the target genes of NFAT2 would thus be informative about the differentiation process. We focused here on chemokine and chemokine receptor genes that act downstream of NFAT2 in RAW264 cells as well as osteoclast precursors prepared from bone marrow cells. MATERIALS AND METHODS: RAW264 mouse monocyte/macrophage line cells were cultured with or without cyclosporin A (CsA) in the presence of RANKL or glutathione S-transferase (GST). Osteoclast precursors were prepared from bone marrow cells. RANKL-inducible and CsA-suppressible genes were searched for by microarray analysis, and expression was confirmed by quantitative RT-PCR. Promoter activity was measured by luciferase gene reporter assay. Short interfering (si)RNA for CCR1 was introduced in RAW264 cells. Cell migration activity was examined using a Boyden chamber assay. RESULTS AND CONCLUSIONS: We identified the chemokine receptor gene CCR1 as a gene showing significant differential expression profiles in osteoclastogenesis in the presence versus the absence of CsA, an inhibitor of NFAT. This property was unique to CCR1 among the chemokine and chemokine receptor genes examined in both RAW264 and bone marrow cells. The upstream regulatory region was isolated from CCR1, and its RANKL-dependent and CsA-suppressible promoter activity was confirmed. The functional significance of CCR1 was assessed by monitoring the migration of cells in a transwell migration assay, and this activity was abolished when either CsA- or CCR1 siRNA-treated cells were used. Moreover, treatment with a Galpha inhibitor pertussis toxin (PTX) or methiolynated-regulated on activation, normal T cells expressed and secreted (Met-RANTES), an antagonist of CCR1, suppressed multinucleated cell formation in the bone marrow cell system. Together, these results suggest that the CCR1 signaling cascade is under the control of NFAT2 and seems to enhance the migration of differentiating osteoclasts.     

Prognostic factors in patients with ipsilateral pulmonary metastasis from non-small cell lung cancer.

OBJECTIVE: Pulmonary metastasis of non-small cell lung cancer is classified as an advanced disease stage, with limited indications for surgical treatment. However, the prognosis of patients with pulmonary metastasis of non-small cell lung cancer is better than that of patients with distant metastases. The purpose of the present study was to analyze and detect possible prognostic factors in surgically treated patients with ipsilateral pulmonary metastasis of non-small cell lung cancer. METHODS: Among 1198 patients with non-small cell lung cancer who underwent surgery at Kurashiki Central Hospital (Okayama, Japan) from April 1982 to March 2004, a total of 48 (4.0%) patients with pathologically diagnosed ipsilateral pulmonary metastasis were retrospectively evaluated. The median follow-up time was 20.5 months (range 1-103 months) and 37 patients (77.1%) were completely followed up until their death or more than 5 years after the operation. RESULTS: Among the 48 patients, 31 (64.6%) patients had metastatic nodules in the same lobe as the primary tumor (PM1) and 17 (35.4%) patients had metastatic nodules in different ipsilateral lobes (PM2). There was no significant difference in survival between patients with PM1 and the other patients with pT4-stage IIIB, or between patients with ipsilateral PM2 and the other patients with stage IV. Univariate analysis of postoperative survival stratified according to clinicopathologic factors revealed significant differences for the radicality of resection (complete vs. incomplete), tumor size (0-30 vs. >30mm) and pathological nodal (pN) factor (among pN0, pN1 and pN2-3). Multivariate analysis revealed that tumor size (0-30 vs. >30mm) and pN factor (pN0-1 vs. pN2-3) were independent prognostic factors. CONCLUSIONS: The results of our study suggest that undergoing a complete resection, having a tumor size of 30mm or less and having no mediastinal lymph node metastases were better prognostic factors for surgically treated patients with ipsilateral pulmonary metastasis of non-small cell lung cancer.     

Scaling Lichenoid Eruptions and Sjögren-like Syndrome: Manifestations of Nonfatal Postoperative Transfusion-Associated Graft-versus-Host Disease?

We report a case of an 81-year-old woman in whom lichenoid eruptions and Sjögren-like sicca syndrome developed 45 days after cholecystectomy. During surgery, one unit (130 ml) of unirradiated packed red blood cells from a male donor was transfused. The lichenoid eruptions cleared up with exfoliation; however, sicca symptoms remained during the follow-up period of four years. Histological examinations of both skin and lip biopsy specimens were in agreement with those of graft-versus-host disease (GVHD). A Y-chromosomal body was identified in the lymphocytes in the skin lesion by staining with quinacrine dihydrochloride and in the lip lesion by a method with in situ hybridization. The findings suggest that this case demonstrated the manifestations of non-fatal transfusion-associated GVHD.