Phase I--II evaluation of combination cyclophosphamide, 5-fluorouracil, hexamethylmelamine, and prednisone in advanced breast cancer

A four-drug combination of intermittent high-dose cyclophosphamide with 5-fluorouracil, hexamethylmelamine, and prednisone was given to 19 patients with advanced breast cancer. Objective response was documented in 7 of 18 evaluable patients. The median duration of response was 99 days. Response was observed in 6/7 patients without visceral disease and 1/11 patients with visceral disease. Toxicity was acceptable and no life-threatening toxicity was observed. Three patients have received the four-drug combination for more than 1 year without serious side effects. This regimen may serve as an alternative treatment for patients without visceral metastasis who have failed to respond to other combination chemotherapy regimens.     

Scrub typhus encephalomyelitis with prominent focal neurologic signs

BACKGROUND: Encephalomyelitis with prominent focal neurologic signs and associated neuroradiologic abnormalities has not been previously described in scrub typhus. CASE DESCRIPTION: A 22-year-old woman was admitted because of fever and an altered mental state. Neurologic examination revealed bilateral sixth and seventh nerve palsies, bilateral gaze evoked nystagmus, anarthria, dysphagia, quadriparesis, and sensory level at T1. Serum and cerebrospinal fluid samples were positive for tsutsugamushi antibody. The patient's magnetic resonance images demonstrated the lesions responsible for the neurologic dysfunctions: in the lower brainstem, cerebellar peduncles, and spinal cord. It was interesting that the gray matter of the spinal cord was predominantly involved. CONCLUSIONS: The recognition of unusual manifestations and the clinical suspicion of this treatment-responsive disease may be important, particularly in the face of increasing international and intranational travel.     

Adult bacterial meningitis in Southern Taiwan: epidemiologic trend and prognostic factors

In two investigative phases over a 13.5-year study period (January 1986-June 1999), 202 adult patients with culture-proven bacterial meningitis were enrolled in this study. In order to determine the epidemiologic trend, prognostic factors and therapeutic results for this disease. Klebsiella pneumoniae (K. pneumoniae), Pseudomonas aeruginosa, and Streptococcus pneumoniae were the three most commonly revealed pathogens, accounting for about 48% of the episodes. Although there was a change in relative frequency for the pathogens, K. pneumoniae remained the most prevalent during the two periods studied (January 1986-December 1992 and January 1993-June 1999). Multiantibiotic resistant strains have been in evidence since their appearance in 1994, with most of our patients acquiring their infection nosocomially. The overall mortality rates during the two periods were 40% and 34%, respectively. In stepwise logistic regression analysis, only initial conscious level, appropriate antibiotic therapy and septic shock were independently associated with mortality, after adjustment for other potentially confounding factors. Initial empirical antibiotics with both third-generation cephalosporin and penicillin G, should be considered for the majority of meningitis cases resulting from infection with Gram-negative bacilli and streptococcal species. Besides the evolution of newer pathogens, there has been increasing incidence for nosocomially acquired bacterial meningitis for patients postneurosurgery, with the emergence of resistant strains presenting a therapeutic challenge in recent years. Vancomycin and imipenem/cilastatin should be considered as the initial empirical antibiotics of choice for the treatment of this special group of patients.     

Norepinephrine regulation of growth hormone release from goldfish pituitary cells. I. Involvement of alpha2 adrenoreceptor and interactions with dopamine and salmon gonadotropin-releasing hormone

Adrenergic regulation of growth hormone (GH) release in the goldfish was examined in vitro using dispersed goldfish pituitary cells under column perifusion. Norepinephrine and epinephrine suppressed basal GH release from goldfish pituitary cells in a reversible and dose-dependent manner. At high doses, a transient rebound of GH release was observed after termination of norepinephrine and epinephrine treatment. In this study, the dose-dependence of adrenergic inhibition on basal GH release was mimicked by the alpha2 agonists clonidine and UK14304. Basal GH secretion, however, was not affected by the beta agonist isoproterenol and alpha1 agonist methoxamine. In addition, the inhibitory actions of norepinephrine and clonidine on basal GH release were blocked by the alpha2 antagonists yohimbine and RX821002. The beta antagonist propranolol and alpha1 antagonists prasozin and benoxathian were not effective in this respect. Salmon gonadotropin-releasing hormone (sGnRH) and dopamine, two known GH-releasing factors in fish, stimulated GH release from goldfish pituitary cells and their GH-releasing actions were inhibited by simultaneous treatment with norepinephrine. Furthermore, the GH rebound after norepinephrine treatment was significantly enhanced by prior exposure to sGnRH and this effect was not observed with dopamine treatment. These results, taken together, suggest that in the goldfish adrenergic input at the pituitary level inhibit basal GH release through activation of alpha2 adrenoreceptors. This alpha2 inhibitory influence may interact with dopaminergic and GnRH input to regulate GH secretion from goldfish pituitary cells. The 'post-inhibition' GH rebound after NE treatment and its sensitivity to sGnRH potentiation may also represent a novel mechanism for GH regulation in fish.     

Norepinephrine regulation of growth hormone release from goldfish pituitary cells. II. Intracellular sites of action

Previous results suggest that norepinephrine decreases growth hormone (GH) release in goldfish by means of alpha-2 adrenoceptor activation. The intracellular mechanisms by which norepinephrine inhibits GH release were examined in the present study using dispersed goldfish pituitary cells. In 2-h static incubation experiments, norepinephrine and the alpha-2 agonist clonidine decreased basal GH release and the GH responses to stimulation by the dopamine D1 agonist SKF38393 and two native gonadotropin-releasing hormones (GnRH). Norepinephrine also reduced GH responses to the adenylate cyclase activator forskolin, two protein kinase C (PKC) activators (phorbol ester and synthetic diacylglycerol), and two Ca2+ ionophores (ionomycin and A23187). Similarly, norepinephrine applied as a 1-h pulse in cell column perifusion experiments reduced basal GH release and abolished the GH response to a 5-min pulse of arachidonic acid. In goldfish, D1-stimulated GH release is mediated by AC-, arachidonic acid-and Ca2+-dependent pathways, whereas GnRH action is coupled to PKC-and Ca2+-dependent mechanisms. These results suggest that norepinephrine activation of alpha-2 receptors inhibits ligand-induced GH secretion by actions subsequent to activation of these second messenger cascades. To further characterize norepinephrine mechanisms of action on unstimulated hormone release, the ability of norepinephrine and an alpha-2 agonist to affect activation of two second messenger cascades under basal conditions was also investigated. Static incubation with clonidine reduced cAMP production in a time-and dose-dependent manner, suggesting that norepinephrine inhibitory action can also be expressed at the level of cAMP production. Resting intracellular free calcium levels in single, identified goldfish somatotropes was unaffected by norepinephrine. However, the inhibitory effects of norepinephrine on basal GH secretion was not observed in the presence of a voltage-sensitive Ca2+ channel agonist. Whether these channels are targets for norepinephrine action on unstimulated GH release requires further investigation.     

Community acquired methicillin-resistant Staphylococcus aureus hand infections: case reports and clinical implications

We report a series of 4 cases of community acquired methicillin-resistant Staphylococcus aureus hand infections in patients without risk factors. Methicillin-resistant S aureus infections commonly involve the skin and soft tissue; therefore, hand infections may become more common as the prevalence of this pathogen increases. Hand surgeons must be aware of this emerging pathogen and obtain appropriate tissue cultures to diagnose and effectively treat this infection.     

胆管结石乳头局部组织中血管活性肠肽和一氧化氮合酶表达的改变及意义

目的 探讨胆管结石患者乳头局部组织中血管活性肠肽(VIP)和一氧化氮合酶(NOS)表达的改变及意义。方法 选择68例进行逆行胰胆管造影和/或乳头括约肌切开术的胆管结石患者,采用内镜下活检乳头局部组织。常规石蜡包埋,连续切片,免疫组化SABC法检测VIP及NOS。对照组为门诊胃镜检查胃粘膜大致正常者。结果 结石组乳头粘膜内 VlP和NOS阳性产物与对照组相比较显著降低(P相似文献   

静脉溶栓治疗高龄急性心肌梗死患者的临床探讨

目的　探讨静脉溶栓疗法对高龄急性心肌梗死患者的疗效及安全性。 方法　将 82例高龄急性心肌梗死患者随机分为溶栓组和常规治疗组。溶栓组 40例 ,采用尿激酶静脉溶栓加皮下注射低分子肝素钙。常规治疗组 42例 ,除不用尿激酶及低分子肝素钙外 ,其余治疗均与溶栓组相同。 结果　 血管再通率溶栓组为6 5 %(2 6 / 40 ) ,常规治疗组为 14.3%(6 / 42 ) ,两组血管再通率比较差异具有显著性 (P <0 .0 5 )。溶栓组未见严重出血等并发症。住院 4周内病死率为 5 %。而常规治疗组病死率为 2 3.8%(10 / 42 ) ,两组比较具有显著差异性(P <0 .0 5 )。 结论　 尿激酶静脉溶栓治疗高龄急性心肌梗死可以提高冠脉再通率 ,降低死亡率和改善预后 ,是可行性治疗措施。