Dorsomedial hypothalamic nucleus neurons integrate important peripheral feeding-related signals in rats

Several studies have implicated the dorsomedial hypothalamic nucleus (DMN) in regulation of feeding behavior and body weight, but clear mechanisms by which it controls food intake are not well understood. We report the results of the present study, which showed that the DMN receives important peripheral short- and long-term feeding-related afferent signals, including gastric vagal, glycemia, and cholecystokinin (CCK) inputs, as well as from leptin, an adipostatic signal that forcefully inhibits food intake and increases metabolic rate. Among the 279 DMN neurons recorded, 173 (62.0%) responded to stimulation of gastric vagal nerves. Also, of the 123 DMN neurons responsive to gastric vagal stimulation that were tested with the administration of intravenous glucose, 75 (61.0%) were identified as being glycemia sensitive. Moreover, it is noteworthy that of the 23 DMN neurons that responded to both gastric vagal and intravenous glucose stimulation, most (19 of 23, 82.6%) were sensitive to circulating leptin, and some neurons (n = 7) were also responsive to systemic CCK, suggesting that gastric vagal, glycemic, CCK, and leptin inputs converge on single DMN neurons. Furthermore, synergistic interactions between leptin and glucose on single DMN neurons were observed (n = 6). These results demonstrate that those important peripheral feeding-related gastric vagal, glycemic, CCK and leptin signals not only reach the DMN but also interact on single DMN neurons, suggesting that the DMN may not just function as a relay station, but independently integrate the short-term and long-term feeding-associated information and actively participate in the direct regulation of feeding behavior.     

乳腺癌根治术中保留肋间臂神经的临床研究

目的探讨乳腺癌根治术中保留肋间臂神经的临床价值。方法45例乳腺癌患者随机分为观察组（22例）及对照组（23例）,观察组在施行乳腺癌根治术中保留肋间臂神经,对照组按常规进行乳腺癌根治术,随访半年至6年以观察两组患者患侧肢体感觉障碍情况及局部复发率。结果观察组患者发生患侧肢体皮肤感觉障碍1例（4．5％）,与对照组的17例（73．9％）相比较,差异有统计学意义（Χ^2=20．79,P〈0．01）;两组均未发现局部复发病倒。结论乳腺癌根治术中保留肋间臂神经,不增加局部复发率,可提高患者术后生活质量,减少患侧肢体感觉障碍。     

显微外科在治疗急性周围神经创伤中的价值

目的：探讨显微外科在急性周围神经创伤治疗中的价值。方法：对我院收治的外周神经创伤196例显微手术治疗效果进行对比研究。结果：显微手术对急性周围神经创伤治疗的手术优良率达91％,3个月内达55％,3个月以上仅25％。结论：显微外科手术治疗急性周围神经创伤疗效较好,为临床提供了有价值的参考。     

Vibrotactile threshold measurement for detecting peripheral neuropathy: defining variability and a normal range for clinical and research use

Aims/hypothesis We aimed to define normal ranges for vibration sense as measured by vibratory perception thresholds (VPTs) using biothesiometry. Methods We performed biothesiometry in a community-dwelling sample of 901 people aged 55 to 85 years who did not have diabetes. We quantitated the variation between repeat measures using analysis of variance and Bland–Altman plots. We also plotted the age- and sex-specific reference ranges. Results We found small but statistically significant differences between repeat measures using the ascending and descending method of limits. Statistically higher vibration thresholds were noted on the right arm and leg compared with the left. Significantly higher vibration thresholds were also seen in men vs women for both lower limbs. We also defined sex-specific reference intervals (normal ranges) for biothesiometry for older persons and quantitated the increase in vibration threshold with increasing age. Conclusions/interpretation For reliability, it may be sufficient to obtain the average of two ascending measures separated by at least 1 min in just the right hand or right foot, since this is usually the one with the higher threshold. Although identical reference ranges can be used for men and women for the upper limb, there are significant differences in the lower limbs. The major determinant of VPT is age: we have established age-specific norms for VPT testing for adults between 55 and 85 years of age.     

High-dose chemotherapy and autologous stem cell transplantation for peripheral T-cell lymphoma: complete response at transplant predicts survival

Although the role of high dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) in the treatment of aggressive lymphoma has been established in several large prospective studies, its effectiveness in patients with peripheral T cell lymphoma (PTCL) has not been defined. We aimed to evaluate the efficacy of HDT and ASCT and prognostic factors for survival in patients with PTCL. We retrospectively analyzed the results of 40 PTCL patients treated with HDT and ASCT at Asan Medical Center between January 1995 and December 2005. Twenty patients had PTCL-U (peripheral T cell lymphoma, unspecified), 10 had extranodal natural killer/T cell lymphoma, 5 had anaplastic large cell lymphoma, 3 had angioimmunoblastic T cell lymphoma, 1 had hepatosplenic γσ T cell lymphoma, and 1 had disseminated mycosis fungoides. Disease status at transplant was complete response (CR)1 in 3 patients, CR2 or greater in 8, partial remission in 25, and refractory in 4. At a median follow-up of 16 months (range, 5 to 135 months) for surviving patients, the median overall survival (OS) was 11.5 months and the 1-year probability of survival was 46.1%. The median event free survival (EFS) was 3.6 months (95% confidence interval, 2.5 to 4.8 months). Ten patients (25%) remain alive without evidence of disease. The median OS of 11 patients with CR at ASCT was not reached; of these, 7 patients (63.6%) were alive with CR. In multivariate analysis, CR at ASCT was a prognostic factor for EFS (P = 0.025) and OS (P = 0.027) and normal lactate dehydrogenase (LDH) at ASCT was a prognostic factor for improved OS (P = 0.025). Chemosensitive patients with PTCL who achieved CR before ASCT seem to benefit from HDT and ASCT. Pretransplant values of LDH had potential to predict the survival.     

Superiority of the limb leads over the precordial leads on the 12-lead ECG in monitoring fluctuating fluid overload in a patient with congestive heart failure

A 78-year old woman with congestive heart failure had fluctuating peripheral edema and weights while hospitalized and was subsequently followed in the cardiac clinic. Sums of the amplitudes of the QRS complexes for the leads I + II (∑QRS_{I + II}), the 6 limb leads (∑QRS_6L), the 6 precordial leads (∑QRS_V1-V6), and all 12 leads (∑QRS_12L) were calculated. Analysis showed that ∑QRS_{I + II} and ∑QRS_6L correlated very well with corresponding weights (r = 0.78, P .01 and r = 0.75, P = .02, respectively), whereas ∑QRS_V1-V6 and ∑QRS_12L did not (r = 0.20, P = .60 and r = 0.47, P = .20, respectively). The reason for the poor correlation of the latter two was the erratic values of ∑QRS_V1-V6 in serial electrocardiogram recordings. ∑QRS_{I + II} and ∑QRS_6L are useful for serially following patients with congestive heart failure and peripheral edema.     

Using ankle-brachial index to detect peripheral arterial disease: prevalence and associated risk factors in a random population sample

Background and aimThe ankle-brachial index (ABI) is being used increasingly to diagnose peripheral arterial disease (PAD) that predicts cardiovascular morbidity and mortality. The aim of this study is to determine the prevalence of PAD and associated risk factors in a Spanish random population sample of age ≥40.Methods and resultsPAD is defined as an ABI < 0.9 in either leg. 784 participants of age ≥40 were randomly selected in a Spanish province. 55.4% of them were female. The prevalence of PAD in this sample was 10.5% (95% confidence interval (CI) 8.4–12.8); 9.7% in females and 11.4% in males. In logistic regression analyses, adjusted for age and gender, smoking per 10 pack-years (odds ratio (OR) 1.40, 95% CI 1.23–1.58), hypertension (OR 1.85, 95% CI 1.05–3.28), hypercholesterolemia (OR 1.76, 95% CI 1.04–2.98), and diabetes (OR 1.80, 95% CI 1.04–3.11) were positively associated with prevalent PAD. More than 91% of persons with PAD had one or more cardiovascular disease risk factors.ConclusionsWe conclude that in our study hypertension, hypercholesterolemia, diabetes mellitus and smoking are associated with PAD. The majority of individuals with PAD had at least one important cardiovascular risk factor advanced enough to be considered eligible for an aggressive treatment.     

Assessment of lower limb ischemia with measurement of skin perfusion pressure in patients on hemodialysis

Measurement of skin perfusion pressure (SPP) using laser Doppler has become available for the assessment of peripheral arterial disease. We studied whether measurements of SPP can be used to identify hemodialyzed patients with peripheral arterial disease by comparing it with measurements of the ankle brachial pressure index (ABI). The ABI at rest and the SPP in the foot were measured in 59 Japanese hemodialyzed patients (118 limbs). Twenty-one patients had diabetes mellitus. Five had intermittent claudication; however, 20 patients were accompanied by other exertional leg symptoms. The SPP could not be measured in three limbs because of involuntary movement due to previous stroke or restless leg syndrome. The SPP was correlated with the ABI. Depending upon these results of the ABI, the 114 limbs from which both the ABI and the SPP could measured were divided into three groups: (A) ABI > or = 1.3, (B) 0.9 < or = ABI < 1.3, and (C) ABI < 0.9. The average SPP of group C was significantly decreased among the three groups. All subjects of the three groups were divided into an extra two groups according to the presence of diabetes (non-diabetes groups, -I; diabetes groups, -II). The average SPP of group B-II was significantly decreased compared with those of group B-I. The SPP measurement is a noninvasive, useful screening method for limb ischemia that can be applied to exercise tolerance limited patients. The SPP measurements are expected to be useful for the evaluation of limb ischemia in hemodialyzed patients at risk.     

Live to the rhythm, slave to the rhythm

Circadian rhythms in health and disease have most often been described in terms of their phases and amplitudes, and how these respond to a single exposure to stimuli denoted as zeitgebers. The present paper argues that it is also important to consider the 24-h regularity in the repeated occurrence of the zeitgebers. The effect of the regularity of stimulation by light, melatonin, physical activity, body temperature, corticosteroids and feeding on synchronization within and between the central circadian clock and peripheral oscillators is discussed. In contrast to the phase shifts that can be recorded acutely after a single zeitgeber pulse, the effects of irregularly versus regularly timed zeitgeber can be studied only in long-term protocols and may develop slowly, which is a possible reason why they have received relatively little attention. Several observations indicate a reciprocal relation between the robustness of the endogenous circadian timing system and its dependency on regularly timed zeitgebers. Especially at old age and in disease, proper functioning of the circadian timing system may become more dependent on regularly timed exposure to zeitgeber stimuli. in such conditions, regularly timed exposure to zeitgeber appears to be highly important for health. After a concise introduction on inputs to the central and peripheral oscillators of the circadian timing system, the paper discusses the responses of the circadian timing system and health to (1) a chronic lack of zeitgeber stimuli; (2) fragmented or quasi-ultradian stimuli and (3) repeated phase shifts in stimuli. Subsequently, the specific relevance to aging is discussed, followed by an overview of the effects of experimentally imposed regularly timed stimuli. Finally, a possible mechanism for the gradually evolving effects of repeated regularly timed stimuli on the circadian timing system is proposed.     

<Emphasis Type="BoldItalic">Nf1</Emphasis> expression is dependent on strain background: implications for tumor suppressor haploinsufficiency studies

Neurofibromatosis type 1 (NF1) is the most common cancer predisposition syndrome affecting the nervous system, with elevated risk for both astrocytoma and peripheral nerve sheath tumors. NF1 is caused by a germline mutation in the NF1 gene, with tumors showing loss of the wild type copy of NF1. In addition, NF1 heterozygosity in surrounding stroma is important for tumor formation, suggesting an additional role of haploinsufficiency for NF1. Studies in mouse models and NF1 families have implicated modifier genes unlinked to NF1 in the severity of the disease and in susceptibility to astrocytoma and peripheral nerve sheath tumors. To determine if differences in Nf1 expression may contribute to the strain-specific effects on tumor predisposition, we examined the levels of Nf1 gene expression in mouse strains with differences in tumor susceptibility using quantitative polymerase chain reaction. The data presented in this paper demonstrate that strain background has as much effect on Nf1 expression levels as mutation of one Nf1 allele, indicating that studies of haploinsufficiency must be carefully interpreted with respect to strain background. Because expression levels do not correlate entirely with the susceptibility or resistance to tumors observed in the strain, these data suggest that either variation in Nf1 levels is not responsible for the differences in astrocytoma and peripheral nerve sheath tumor susceptibility in Nf1-/+;Trp53-/+cis mice, or that certain mouse strains have evolved compensatory mechanisms for differences in Nf1 expression.