Repeated cocaine administration differentially affects NMDA receptor subunit (NR1, NR2A-C) mRNAs in rat brain

We investigated the effects of intermittent intraperitoneal (i.p.) injections of cocaine (20 mg/kg) on subunit mRNAs of N-methyl-D-aspartate (NMDA) receptors (NR1/NR2A-2C) in the rat brain by in situ hybridization using phosphor screen analysis. The level of NR1 subunit mRNA significantly increased in hippocampal complexes 1 h after a single i.p. injection of cocaine. After repeated cocaine injection, the mean scores of stereotyped behavior were increased with the number of injections. The level of NR1 subunit mRNA was obviously decreased in the striatum and cortices 24 h (early withdrawal) after a final injection following 14 days of subchronic administration. During the early withdrawal period, the amount of the NR1 subunit decreased in the nucleus accumbens, globus pallidus, and subiculum. In the dentate gyrus, the NR1 mRNA level significantly increased during early withdrawal in rats subchronically treated with cocaine. Levels of NR2B subunit mRNA were reduced in the cortices and striatum. During late withdrawal from cocaine, the level of NR2C subunit mRNA in the cerebellum was also reduced. These findings suggest that the disruption of NR1, NR2B, and NR2C subunits in the discrete brain regions occurs under the cocaine-related behavioral abnormalities and would be closely implicated in the initiation and expression of behavioral sensitization induced by repeated cocaine administration. Further studies on the changes in non-NMDA receptors are required to elucidate the biological significance of glutamate receptors for the mechanisms underlying the development of behavioral sensitization.     

Caregiver burden in mobile and non-mobile demented patients: a comparative study

OBJECTIVES: to identify the impact of behavior disturbances on subjective burden of caregivers in demented patients attending day care services. METHODS: subjects were 379 primary caregivers of randomly sampled demented patients living at home, who attended geriatric day care programs. The caregiver burden of the mobile and non-mobile demented patients were measured using the Zarit Caregiver Burden Interview (ZBI). The Mini-Mental State Examination (MMSE) and the Personal Self-Maintenance Scale (PSMS) were used to assess the patients' condition. The Troublesome Behavior Scale (TBS), originally developed in Japan, was used to assess the frequency of behavior disturbances exhibited by patients. RESULTS: the caregivers of the mobile demented patients reported greater caregiver burden compared to those of the non-mobile demented patients. The frequency of behavior disturbance was significantly higher in the mobile patients than the non-mobile patients. For the mobile patient caregivers, wandering, interfering, aggression and repetition were the predictors of caregiver burden. For the non-mobile patient caregivers, 'repeating same questions and/or clinging' was the only predictor of caregiver burden. CONCLUSION: the caregivers of the mobile demented patients reported higher burden due to the patients' behavior disturbance compared to those of the non-mobile patients. These findings indicate a need for further development of interventions to prevent behavior disturbances that are especially burdensome for caregivers.     

Incidence and duration of hoarseness following endotracheal intubation

The incidence and duration of hoarseness following tracheal intubation with general anesthesia were studied retrospectively from November 1998 to October 2000 in postanesthetic clinic of Nara Medical University. Total number of patients was 3977 and 37.1% of them complained of hoarseness. Most of there patients recovered within three days after surgery but in 4.2% the hoarshness persisted over ten days and in 0.7% persisted over one month after surgery. Most of these persistent hoarseness were considered to have originated from surgical procedures (such cervical, pulmonary, cardioaortic operation, etc.) and those following only tracheal intubation recovered within two months after surgery. The hoarseness decreased the satisfactory level for anesthesia in 1.0% of total patients and 12.8% of patients with persistent hoarseness. We consider that preoperative explanation and postoperative communication by anesthesiologists are important.     

Evaluation of the management of blunt renal trauma and indication for surgery

OBJECTIVES: Appropriate management of renal trauma is still controversial. Many of the patients have minor injuries and conservative treatment can achieve excellent outcomes without any complications. For major injuries of deep lacerations or ruptures, we have been performing early surgical treatment to salvage the kidney in the selected cases after the precise evaluation of the injury. To obtain the optimal management options, we evaluated the clinical results of our procedures. PATIENTS AND METHODS: We conducted a retrospective study, which included 106 cases of blunt renal trauma with evident etiology over the past 22 years and 9 months. The severity of the injury was evaluated mainly by CT scanning. The indication of renal exploration included persistent renal bleeding, large hematoma around the kidney, dislocated fragments, nonviable tissue, massive urinary extravasation and vascular injury. With the patients who required an operation, we first controlled the bleeding by clamping the hilar vessels. Then, the final decision whether to repair or remove the kidney was made based on the direct inspection of the injured kidney after the complete removal of the hematoma. The severity of renal trauma was classified by the classifications found in The Organ Injury Committee of the American Association for the Surgery of Trauma. RESULTS: Sixty-three patients were managed conservatively without any interventions, while 22 surgical repairs and 21 nephrectomies were performed. Of the 63 patients, 35 patients (81.4%) were operated on within 2 days after the injury. Judging from systolic blood pressure, red cell count, blood loss during surgery and transfusion requirements, surgically treated patients were more severely injured than conservatively treated patients. And nephrectomized patients than surgically repaired patients. All the surgically repaired cases were confirmed to have preserved renal functions postoperatively. In all of the 50 patients with Grade I injuries, conservative treatment was successful. Eight out of the 19 Grade II and III cases, who were indicated for kidney exploration because of multiple lacerations or considerable bleeding, were also successfully repaired. Localized hematoma with no urine leakage, even when it was large, settled spontaneously without complication. For the 37 Grade IV and V injuries, including 4 cases with hilar injuries, we implemented conservative procedures on 2 patients, surgical repair on 14 patients and nephrectomy on 21 patients. In the conservatively treated cases, one deep laceration with relatively large, but localized, hematoma, and minimal urine extravasation healed spontaneously. Atrophy of the segment and hypertension developed in the other ruptured kidney with dislocated fragments, large hematoma and urine leakage. This kidney, which also required later surgical exploration, did have good parenchymal blood flow. Hilar injury cases were all resulted in nephrectomy. CONCLUSION: In most of our cases the indication for surgical exploration or nephrectomy based on our criteria seemed to be properly decided. Several cases, though, might have received overtreatment. Recent advances in evaluations and strategies of renal trauma have decreased the need for surgical exploration. This may have overreached the indication for conservative management. Severely injured kidneys may be managed conservatively because in most cases bleeding settles after the full formation of large hematoma within the Gerota's fascia. In such cases, though, no one can predict whether the injury will heal spontaneously or not, and, moreover, whether a complication will develop or not. We think that the optimal management of the patient requires an accurate evaluation of the injured kidney. Therefore the indication for surgical exploration should be made based on the degree of the injury.     

Alteration of the horizontal mandibular condyle size associated with temporomandibular joint internal derangement in adult females

OBJECTIVES: The purpose of this retrospective study was to analyse the relationship between horizontal size of the mandibular condyle and internal derangement (ID) of the temporomandibular joint (TMJ). METHODS: One hundred and thirty-nine joints in 88 women aged over 18 years were included in this study. The horizontal condylar size was measured in the antero-posterior and medio-lateral (ML) dimensions using axial magnetic resonance (MR) images. Radiological findings of ID were also assessed from MR imaging. RESULTS: The condyles in the joints with permanent disk displacement were smaller than those in joints without displacement in both dimensions (Fisher's protected least significant difference, P<0.05). There were statistically significant correlations between horizontal condylar size in the ML dimension and both disk morphology and radiological stage of ID (Spearman's correlation coefficient by rank, P<0.05). CONCLUSIONS: The results of this study suggest a possible relationship between horizontal condylar size and disk displacement. It is also suggested that the condyle becomes smaller in the ML dimension with advancement of ID.     

Lewy体病患者损伤心肌对^123I-间碘苄胍的摄取情况：Lewy体型痴呆和帕金森病的比较

背景：^123I标记的间碘苄胍（^123I—MIBG）心肌闪烁扫描曾被用以评估Lewy体病（LBD）患者的心脏交感神经去神经支配，LBD包括帕金森病（PD）与Lewy体型痴呆（DLB）。LBD患者的心肌MIBG累积显著减少，表明患者的心脏交感神经系统严重损伤。然而，DLB和PD患者之间的闪烁扫描差异尚不确定。目的：本研究旨在对比在疾病的早期阶段采用^123I—MIBG闪烁扫描所测DLB和PD患者的心脏交感神经功能。方法：在22例早期DLB患者、41例早期原发性PD患者和15例正常对照受试者（年龄与病程与患者相匹配）中进行^123I—MIBG心肌闪烁扫描检查。计算心脏／纵隔对^123I—MIBG的摄取比（H／M）。结果：早期DLB患者心肌对^123I—MIBG的摄取明显低于对照者。DLB患者的平均H／M明显低于PD患者，并且不依赖于Hoehn和Yahr阶段。结论：本研究结果表明，DLB患者心脏交感神经功能即使在疾病的早期阶段就已经严重受损。     

A comparative study of terazosin and tamsulosin for symptomatic benign prostatic hyperplasia in Japanese patients

OBJECTIVE: To compare the efficacy and safety of an incremental-dose regimen of terazosin (1-2 mg daily) and a fixed-dose regimen of tamsulosin (0.2 mg daily), on Japanese patients with symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: This multicentre, single-blind, randomized trial compared terazosin and tamsulosin over 4 weeks, in 61 patients with symptomatic BPH randomly assigned to terazosin (n = 31) or tamsulosin (n = 30). Terazosin 0.5 mg twice daily was administered for 2 weeks, followed by 1 mg twice daily for 2 weeks. Tamsulosin (0.2 mg) was administered once daily for 4 weeks. Symptoms were evaluated using the International Prostate Symptom Score (IPSS), and quality of life (QOL) was assessed subjectively before treatment, and again after 2 and 4 weeks of treatment. Objective measurements taken before and after the treatment period were the maximum (Qmax) and average (Qave) urinary flow rates, and the percentage residual urine volume. Improvement was defined as a 25% decrease from baseline in IPSS, > 1 point increase in QOL score, and > 2.5 mL/s increase in Qmax. Adverse reactions potentially related to the study drugs were recorded throughout the treatment period. RESULTS: Both terazosin and tamsulosin produced statistically significant improvements in subjective and objective variables. Neither treatment affected systolic or diastolic blood pressure or pulse rate. Adverse reactions were noted in four patients (three in the terazosin group and one in the tamsulosin group). However, there was no statistically significant difference in the incidence of adverse effects between the groups. CONCLUSIONS: Despite the limitations of small sample size and relatively short treatment periods, terazosin and tamsulosin were equally effective in the treatment of symptomatic BPH in Japanese patients, using relatively lower doses than those used in Western countries.     

Discrimination of histamine H1 and muscarinic receptor-mediated signalling pathways by phorbol ester in human astrocytoma cells

1. Histamine H1 receptor-mediated signalling was compared with muscarinic receptor-mediated signalling in 1321N1 human astrocytoma cells. 2. Short-term (2 min) treatment of cells with phorbol 12-myristate 13-acetate (PMA) resulted in a reduction of increases in intracellular Ca2+ ([Ca2+]i) induced by carbachol or histamine. 3. Carbachol-induced increases in [Ca2+]i were 10-fold more sensitive to PMA than the histamine-induced increases. 4. When cells were treated with PMA for 48 or 72 h (long-term treatment), protein kinase C (PKC) was down-regulated and PMA did not inhibit carbachol-induced increases in [Ca2+]i. 5. Histamine-induced increases in [Ca2+]i were significantly reduced by long-term treatment with PMA. 6. These findings suggest that the signalling pathways mediated by histamine H1 and muscarinic receptors can be distinguished by using PKC in 1321N1 human astrocytoma cells.     

Phase II study of concurrent chemotherapy and radiotherapy for unresectable stage III non-small-cell lung cancer: Long-term follow-up results. Japan Clinical Oncology Group Protocol 8902

Background:Although chemoradiotherapy is standard treatment forunresectable stage III non-small-cell lung cancer (NSCLC), few long-termsurvival data exist. Patients and methods:Between October 1989 and December 1991, 74patients with histologically or cytologically proven NSCLC, unresectable stageIIIA or IIIB, were entered into this study. Seventy patients were eligible andevaluable for response, toxicity, and survival analysis. Chemotherapyconsisted of cisplatin (100 mg/m² on days 1, 29, and 57) andvindesine (3 mg/m² on days 1, 8, 29, 36, 57, and 64). Thoracicradiotherapy was administered for two weeks (2 Gy given 10 times, fivefractions per week), and after a 14-day rest period, the previous schedule ofradiotherapy was repeated for two weeks. A 10-Gy to 20-Gy dose of radiotherapywas administered during the third cycle of chemotherapy. Results:Of the 70 evaluable patients, 1 (1.4%) hada complete response (CR) and 51 (72.9%) had a partial response (PR).The median survival time was 14.8 months, and the five-year survival rate was14.8%. The major toxicity was leukopenia ( grade 3, 93%).Other toxicities grade 3 included anemia (34%),nausea/vomiting (27%), alopecia (7%), thrombocytopenia(4%), and serum creatinine elevation (1%). Treatment relateddeath occurred in two patients (2.8%). One patient died of pneumoniaand pneumothorax, and the other of hemoptysis. Conclusions:Concurrent chemotherapy and radiotherapy has thepotential to provide long-term survival with acceptable toxicities.     

Non-randomized study on the effects of preoperative radiotherapy and daily administration of low-dose cisplatin against those of radiotherapy alone for oral cancer--effects on local control, control of metastases, and overall survival

Cisplatin is a known radiation modifier. Our previous study suggested that daily administration of low-dose cisplatin enhanced the efficacy of radiotherapy against primary oral squamous carcinoma. In this paper, we follow the patients who participated in the previous study and survey the benefit of combination low-dose cisplatin in improving local control, prevention of metastases, and overall survival. This study included patients with surgically resectable advanced oral tumors. Ten patients underwent preoperative radiotherapy of 30-40 Gy/15-20 days with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m2). Ten other patients received external radiotherapy alone. All patients then underwent a planned radical tumor resection. No significant difference was see in loco-regional control rates (primary: 86 vs. 88%, neck: 83 vs. 78% at 48 months) or incidence of metastasis (70 vs. 64%) between the two groups. Nor was there a significant difference in the overall survival rate (60 vs. 66%). The results of this study suggest that the concomitant use of daily administration of low-dose cisplatin with preoperative radiation brings no statistically significant benefit in improving local control and survival rate in patients with advanced resectable oral cancer.