Reduced expression of nm23-H1, but not of nm23-H2, is concordant with the frequency of lymph-node metastasis of human breast cancer

The nm23 gene is a potential metastasis-suppressor gene originally identified in a murine melanoma line. Several investigators have reported the probable inverse association of nm23 expression with disease prognosis and/or metastasis. Since there are now 2 known isotypes of human nm23, namely nm23-H1 and -H2, we immunohistochemically examined expression of these isotypes in human breast-cancer tissues using monoclonal antibodies (MAbs) specific for each isotype protein. We also analyzed expression of c-erbB-2 in the same collection of cancer tissues, in order to examine the significance of nm23 expression in comparison with c-erbB-2 expression. Of 130 tumors from breast-cancer patients, 73 (56%) and 69 (53%) positively expressed nm23-H1 and -H2 respectively. Expression of c-erbB-2 was positive in 36 (28%). Expression of nm23-H1, but not nm23-H2, was inversely associated with lymph-node metastasis (p < 0.01). Expression of c-erbB-2 was associated with Tnm stage, tumor size and lymph-node metastasis (p < 0.01, p < 0.05 and p < 0.05 respectively). Overall survival was better (p = 0.014) in patients in whom expression of nm23-H1 was positive than in those in whom it was negative. In multivariate analyses using a Cox's proportional-hazards regression model with 9 variables, nm23-H1 showed the fourth greatest contribution to patient survival following lymph-node metastasis, Tnm stage and menopausal status. No significant contribution was shown for c-erbB-2 expression. nm23-H1, but not nm23-H2, may perform a role in disease prognosis in addition to its participation in cancer metastasis. It may have value for predicting long-term survival of human breast-cancer patients. © 1993 Wiley-Liss, Inc.     

Effects of alcohol infusion on smoking-induced cerebrovascular changes in rat in vivo

The combined effects of alcohol and cigarette smoking on the cerebral circulation are unknown. The current study was designed (1) to compare the acute effects on cerebral vessels of cigarette smoking alone with those of alcohol plus cigarette smoking and (2) to clarify the mechanism or mechanisms underlying the cerebrovascular responses. In pentobarbital-anesthetized, mechanically ventilated Sprague–Dawley rats, we measured pial vessel diameters with the use of a cranial window preparation. Rats, pretreated with alcohol (n = 6; 1 g/kg/h, i.v.; 1-h infusion from t = −60 min to t = 0) or with saline (n = 6), were exposed to 60 puffs per minute of mainstream smoke from a 1 mg-nicotine cigarette. Inhalation of smoke caused pial arterioles to constrict at t = 30 s (8.4%) and, subsequently, to dilate (peak at t = 5–10 min; 18.7%). Pretreatment with alcohol caused pial vasodilation (14.0%), and, after inhalation of cigarette smoke, the pial vasodilation occurred earlier (peak at t = 1–5 min; 30.2%) and was larger, without an initial vasoconstriction. The plasma concentration of thromboxane (TX) B₂ (a stable metabolite of TXA₂) increased after this smoking, and alcohol pretreatment attenuated this increase (protocol as above). Cigarette smoking had a significant biphasic effect on cerebral arteriolar tone. However, alcohol suppressed the initial vasoconstriction, probably, at least in part, by attenuating the smoking-induced TXA₂ production.     

ADULT T CELL LEUKEMIA HISTOLOGICAL CLASSIFICATION AND CHARACTERISTICS

Adult T cell leukemia was classified into two distinct types, monomorphic and pleomorphic, according to their histological and cytological features. The former type is composed of uniform neoplastic cells with round or slightly indented nuclei without any marked deformation. The latter type, on the other hand, occupies a unique position in lymphocytic leukemias with the following characteristics: a) onset in adulthood, b) an acute and subacute course, c) well-differentiated T cell origin of the neoplastic cells, d) pleomor-phism of the neoplstic cells with markedly deformed nuclei, e) difkuse proliferation of the neoplastic cells without nodular pattern, f) histologically heterogeneous features of lymph nodes frequently admixing a cluster of normal lymphocytes, proliferation of macrophages and dendritic cells, and well-developed high endothelium venules, g) high incidence of skin lesions due to the infiltration of neoplastic cells, and h) exclusively limited localization of patients' birth places.     

A new, easy method for putting "U" stitches inside the chest wall

In this report, we describe a new, easy method for putting “U” stitches inside the chest wall. The method does not require extension of the skin incision nor subcutaneous dissection and it minimizes chest wall injury. This method may also be applied to other surgical fields where needles can penetrate the wall of the cavity when it is difficult to stitch from the inside of the cavity.     

Systematic node dissection by VATS is not inferior to that through an open thoracotomy: a comparative clinicopathologic retrospective study

BACKGROUND: Major pulmonary resection with systematic node dissection (SND) for early lung cancer by video-assisted thoracic surgery (VATS) is performed in many institutes, but the feasibility of SND for early lung cancer by VATS remains controversial. The aim of this study was to elucidate the feasibility and safety of SND by VATS. METHODS: Three hundred fifty patients with clinical stage I lung cancer who underwent pulmonary major resection with SND between 1998 and 2003 were enrolled in this study. Of these patients, 191 (VATS group) underwent pulmonary resection with SND by VATS; 159 patients (open thoracotomy [OT] group) did so through anterolateral thoracotomy. The clinical and pathologic data, including the number of dissected nodes in each nodal station, of the 2 groups were compared to evaluate the feasibility of SND by VATS. RESULTS: Pathologic data showed that, in the VATS group, more patients had adenocarcinoma (P = .0078) and fewer patients had advanced factors than the OT group. The greatest tumor diameter was 24.5 mm and 29.6 mm in the VATS group and OT group, respectively (P < .0001). The total number of mediastinal nodes dissected in right upper lobectomy plus right middle lobectomy (RUL+RML), right lower lobectomy (RLL), left upper lobectomy (LUL), and lower left lobectomy (LLL) also did not differ between the 2 groups. The total number of mediastinal nodes dissected in RUL+RML, RLL, LUL, and LLL was 19.7 in the VATS group versus 22.0 in the OT group (P = .122), 23.4 versus 21.0 (P = .241), 14.8 versus 17.5 (P = .123), and 18.8 versus 15.8 (P = .202), respectively. The number of dissected nodes in each nodal station in RUL+RML, RLL, LUL, and LLL was similar between the 2 groups. Operative mortality, morbidity, or recurrence did not differ between the 2 groups. CONCLUSIONS: With regard to the number of dissected nodes, SND by VATS was not inferior to that of OT. SND by VATS is technically feasible and safe, and seems acceptable for clinical stage I lung cancer.     

Myocardial protection by lidocaine hydrochloride in aorto-coronary bypass surgery

Myocardial protective effect of lidocaine hydrochloride on the ischemic myocardium was evaluated by serum (MB-CK) and cardiac function in 48 patients; 24 patients in control (C) and 24 patients in lidocainetreated group (L), who underwent aorto-coronary bypass surgery. Lidocaine hydrochloride, 1 mg/min was administered by continuous drip infusion from initiation of anesthesia, and throughout the operation and postoperative period for 24 hours. There were no significant differences between two groups with regard to duration of cardioplegia and cardiopulmonary bypass, hypothermic level and the number of grafts implanted. Serum MB-CK at 18–24 hours following cardioplegia was 39.5±15.2 I.U. (C) and 14.2±4.0 I.U. (L), (p<0.05). Cardiac index and stroke volume index were significantly increased in the lidocaine-treated group at 24 hours following aortocoronary bypass surgery, as compared to the control group. Lidocaine thus appears to be beneficial in aorto-coronary bypass surgery to prevent ischemic changes in the myocardium. The gist of this paper was read at the 82nd Meeting of the Japanese Surgical Society, April, 1981.     

Local overexpression of HB-EGF exacerbates remodeling following myocardial infarction by activating noncardiomyocytes

Insulin-like growth factor (IGF), hepatocyte growth factor (HGF), and heparin-binding epidermal growth factor-like growth factor (HB-EGF) are cardiogenic and cardiohypertrophic growth factors. Although the therapeutic effects of IGF and HGF have been well demonstrated in injured hearts, it is uncertain whether natural upregulation of HB-EGF after myocardial infarction (MI) plays a beneficial or pathological role in the process of remodeling. To answer this question, we conducted adenoviral HB-EGF gene transduction in in vitro and in vivo injured heart models, allowing us to highlight and explore the HB-EGF-induced phenotypes. Overexpressed HB-EGF had no cytoprotective or additive death-inducible effect on Fas-induced apoptosis or oxidative stress injury in primary cultured mouse cardiomyocytes, although it significantly induced hypertrophy of cardiomyocytes and proliferation of cardiac fibroblasts. Locally overexpressed HB-EGF in the MI border area in rabbit hearts did not improve cardiac function or exhibit an angiogenic effect, and instead exacerbated remodeling at the subacute and chronic stages post-MI. Namely, it elevated the levels of apoptosis, fibrosis, and the accumulation of myofibroblasts and macrophages in the MI area, in addition to inducing left ventricular hypertrophy. Thus, upregulated HB-EGF plays a pathophysiological role in injured hearts in contrast to the therapeutic roles of IGF and HGF. These results imply that regulation of HB-EGF may be a therapeutic target for treating cardiac hypertrophy and fibrosis.     

Effect of pimobendan on cardiopulmonary baroreflex control of sympathetic nerve activity in healthy young men

In order to determine the effect of pimobendan on sympathetic nerve activity and cardiopulmonary baroreflex (CPB), electrocardiogram, direct arterial pressure, central venous pressure (CVP) and cardiac output were recorded along with muscle sympathetic nerve activity (MSNA) in 8 healthy young men. CPB function was evaluated before and 60 min after oral administration of 5 mg pimobendan using the response of MSNA to lower body negative pressure (LBNP) of -5 and -10 mm Hg. The same protocol also was performed during handgrip exercise. Cardiac index, MSNA increased and CVP decreased significantly (p<0.01, respectively), but arterial pressure and heart rate unchanged after pimobendan administration. During LBNP, CVP decreased and MSNA increased significantly. CPB sensitivity was augmented from 5.53+/-0.75 to 8.59+/-0.78 burst incidence/mm Hg after pimobendan administration (p<0.01). Pimobendan did not alter the percentage increase of MSNA during handgrip exercise. In conclusion, pimobendan induces an increase in basal sympathetic nerve activity by decreasing CVP and augmenting CPB sensitivity without changing arterial pressure in healthy young men.     

Effect of baclofen on emesis and 24-hour esophageal pH in neurologically impaired children with gastroesophageal reflux disease

OBJECTIVES: Gastroesophageal reflux disease (GERD) is difficult to control with medical therapy in neurologically impaired children. The gamma-aminobutyric acid type B receptor agonist baclofen was recently reported to reduce reflux in adult patients with GERD by reducing the incidence of transient lower esophageal sphincter relaxations. The current study was undertaken to investigate the effects of baclofen on GERD in neurologically impaired children. METHODS: Eight neurologically impaired children with GERD between 2 months and 16 years were studied. Baclofen (0.7 mg/kg/day) was administered orally or via nasogastric tube in three divided doses 30 minutes before meals for 7 days. The frequency of emesis on and off baclofen were recorded as a measure of clinical impact. Twenty-four-hour esophageal pH monitoring was conducted before and on the seventh day of the administration of baclofen. RESULTS: The frequency of emesis was significantly decreased (P = 0.03). The total number of acid refluxes was significantly decreased both during the entire 24-hour period (P = 0.01) and during the postprandial period (P = 0.049). The number of acid refluxes longer than 5 minutes was significantly decreased during the 24-hour period (P = 0.02). The percentage total time of esophageal pH <4.0 and esophageal acid clearance time were not significantly different during the 24-hour period or during the postprandial period. No adverse effects were observed, except for a slight reduction in muscle tone in one subject. CONCLUSIONS: In this 1-week trial, repetitive administration of baclofen reduced the frequency of emesis and the total number of acid refluxes in neurologically impaired children with GERD.