Pathological complete response to trastuzumab and paclitaxel in a patient with inflammatory local recurrence following breast conserving surgery

We encountered a case of inflammatory local recurrence of breast cancer after breast conserving surgery which attained pathological CR after combination therapy with trastuzumab and paclitaxel. The patient was a 49-year-old premenopausal woman whose left breast cancer(T2N0M0)was treated by breast conserving surgery (Bp+Ax). The pathological diagnosis was scirrhous carcinoma, g, ly1, v0, t2, n0, ER (-), PgR (+) and stage I A. Postoperatively, the residual breast was treated by 50 Gy irradiation followed by hormone therapy(Tamoxifen citrate+LH-RH analog). At 26 months after the surgery, local recurrence developed as inflammatory breast cancer. As the recurrent tumor was confirmed to be HER2-positve (3+ by IHC), combination therapy with trastuzumab and paclitaxel was started. After the 6 courses of pharmacotherapy were completed, she was judged to have clinical CR, and subsequently underwent total breast excision(Bt)and skin grafting. No visible cancer cell was observed in the resected specimens, pathological CR was diagnosed. Postoperatively, the patient is receiving trastuzumab alone every other week, and at present 10 months after the second operation, the patient is in CR status and is visiting the outpatient clinic. No severe side effects (over grade 3) from this therapy have been observed. It is suggested that combination therapy with trastuzumab and paclitaxel for inflammatory local recurrence after breast conserving surgery is a treatment of choice.     

Fracture of the femoral neck, the risk of serious underlying pathology

Between 1997 and 2003, a total of 2223 patients presented to our hospital with the neck of femur fracture. This retrospective study examines the histological results of 90 patients (4%) suspected of having a fracture associated with serious underlying pathology. The mean age at the time of fracture was 80 years (44-97). The patients were divided into four groups. Group I: 34 patients with fracture without history of fall or trauma. Group II: 21 patients with suspicious lesions on the standard pelvic radiograph taken on admission. Group III: 27 patients with past history of malignancy without known bone metastases. Group IV: 8 patients with past history of malignancy and known bone metastases. None of the patients in groups I and II had significant abnormalities other than osteoporosis. Four patients (15%) in group III and six patients (75%) in group IV had metastases on histological examination. It is concluded that only groups III and IV are likely to have fractures due to metastatic disease.     

Co-localization of the heat shock protein and human immunoglobulin G in hepatocellular carcinoma

Elevatedlevelsofserumimmunoglobulinobservedpatientswithcancersofepithelialorigin,includicarcinomasofbreast,colon,andliver1,2havebe interpretedashumoralresponsesofhosttocanc growth.3Recently,Qiuetal4describedindetailth humancancersofepithelialorigin,includingcarcinom ofbreast,colon,liver,lung,establishedepithel cancerlines,produceimmunoglobulinG(IgG)inthe cytoplasm.Undernormalconditions,heatshockprotei(HSPs)havemultiplecellularfunctions,suchasfoldi andtranslocatingnewlysynthesizedproteins.Wh…     

关于重构我国公共卫生体系的政策建议

SARS的爆发流行使我国公共卫生体系存在的问题暴露无疑．但也使越来越多的人开始注意到公共卫生的重要性。从党的十六大提出的“全面建设小康社会”的宏伟目标和十六届三中全会提出的“以人为本、协调发展”的科学发展观出发．运用公共物品理论、卫生保健公平性理论及人力资本理论．就重新构建我国高效、一体化公共卫生体系提出一些政策建议。     

Hepatolithiasis and intrahepatic cholangiocarcinoma: carcinogenesis based on molecular mechanisms

Hepatolithiasis is more frequently seen in East Asian countries than in Western countries, and it is well known to represent a high-risk state for intrahepatic cholangiocarcinoma. Intrahepatic cholangiocarcinoma is an aggressive tumor that shows a dismal outcome even after resection. Cancer results from multistep carcinogenesis; however, the precise molecular mechanisms involved in the genetic alterations in cancer remain unknown. The accumulation of alterations in cancer-related genes leads to disruptions in cell-cycle regulation and also to continuous cell proliferation. The present review provides an overview of cancer-related genes in intrahepatic cholangiocarcinogenesis arising in hepatolithiasis. Further study of molecular mechanisms in hepatolithiasis-related intrahepatic cholangiocarcinoma, and the delineation of the influence of the genes involved should lead to our understanding of cholangiocarcinogenesis.     

d· Ala5 analog of the elastin polypentapeptide. Physical characterization

The d ° Ala₅ analog, (l · Val₁-l · Pro₂-Gly3-l · Val₄-d · Ala₅)_n, of the polypentapeptide (PPP) of elastin is synthesized and characterized by a series of physical methods. Carbon-13 and proton nuclear magnetic resonance spectroscopies are used to verify purity and, by means of solvent dependence of peptide C -O chemical shift and of temperature dependence of peptide NH chemical shift, to establish by comparison with the PPP of elastin the presence and increased stability of the Type II Pro₂-Gly₃ β-turn. The temperature dependence of aggregation in water to form a viscoelastic phase called the coacervate is reported for several concentrations. Comparison of carbon-13 nuclear magnetic resonance spectra obtained under identical conditions for the coacervate states of the PPP of elastin and the d · Ala₅ analog shows the effect of replacing the Gly₅ residue by a d · Ala_s residue to be one of greatly restricting mobility of the polypeptide chain. Scanning electron micrographs, of the coacervate alone and of the coacervate cross-linked and compounded to a Dacron fabric before and after stress-strain studies, are reported which show the d · Ala₅ PPP matrix to rupture during the stresses of drying and of stretching while wet. Thus, the effect of adding a methyl moiety to the Gly₅ residue of the PPP of elastin is to decrease markedly the mobility of the polypeptide chain and to destroy elasticity. The results are presented as a test of the proposed librational entropy mechanism of elasticity of the PPP of elastin.     

Cocaine and pseudococaine: Comparative effects on electrical after-discharge in the limbic system of cats

The effects of cocaine and its dextroisomer pseudococaine on electrical after-discharge (AD) evoked by electrical stimulation of the hippocampus or amygdala were studied in cats with electrodes implanted in the brain. Intravenous injection of cocaine (2.0 to 4.0 mg/kg doses) produced a suppressive effect on the AD while producing low-voltage fast waves (LVFWs) in the electrical activities of the brain (EEG) associated with behavioral excitation. In contrast, pseudococaine at the same dose as cocaine failed to show a significant suppressive effect on the AD except at high doses (5.0 mg/kg). Pseudococaine produced high-voltage slow waves (HVSWs) in the EEG associated with behavioral depression. A linear dose-response relationship was observed for the suppressive effect of cocaine on the AD. The results suggested that the limbic system may be involved as a primary site of action of cocaine in the central nervous system (CNS).     

The problems of memory in aging: Molecular aspects

Mandel, P. :. The problems of memory in aging: Molecular aspects. Drug Dev. Res. 2: 431–432, 1982. It is generally accepted that molecular mechanisms are involved in induction of memory engrams. Thus one may expect that aging, which alters brain metabolism, will also alter memory. The free-radical theory and the cross-linking theory of aging seem to be the most tempting for speculating about memory alterations. The loss of neurons and of their circuits, which probably plays a fundamental role in memory alternation, may result from free-radical effects that alter DNA, induce an increase of repair phenomena, and thus favor mistakes in the repair of DNA.     

Adrenomyeloneuropathy

Summary Histopathological, immunocytochemical, and electron microscopical investigations were carried out in a man with a protracted history of spastic paraparesis, adrenal insufficiency and hypogonadism. Pathological findings were identical with those of the few previously reported cases of adrenomyeloneuropathy (AMN) including cytoplasmic lamellar inclusions consisting of two parallel 2.5 nm leaflets separated by a clear space of variable extent, in the brain, spinal roots, adrenal gland, and interstitial cells of the testis. No inclusions could be found in oligodendrocytes. In brain macrophages they are thought to represent breakdown products of pathological myelin stored in lysosomes, whereas in other localizations they might be an expression of the primary metabolic defect of the cell.Special attention was paid to the pseudosystematic type of fiber tract degeneration in the spinal cord. The dying-back pattern of axonal destruction was interpreted as a possible result of the multisegmental demyelination observed in these tracts.All known hormones could be localized in the pituitary by immunocytochemistry. Corticotrophs and gonadotrophs were numerous. The structural damage of the adrenal cortex and the interstitial cells of the testis is, therefore, considered to result from the inborn error of metabolism on the one hand and from an enhanced stimulation exerted by ACTH and gonadotrophins on the other.This work was supported in part by Grant No. 3.419.78 of the Swiss National Science Fundation     

Transient, powerful pressures are generated in the brain by a rotational acceleration impulse to the head

A rotational acceleration impulse to a head, as occurs at traffic accidents, sport injuries, assaults and falls, induces a diffuse brain damage that eventually could result in persistent neuropsychiatric deficits and neurodegeneration. Emphasis has been concentrated on the relative motion of the brain inside the skull during head impact, whereas less attention has been paid to whether intracranial pressure changes are generated and, if so, the implications thereof. In the present experimental study we investigated in an animal model system, based on rabbits, if a sagittal, anterior-posterior rotational acceleration of a head generated intracranial pressure changes, recorded by fibre optic pressure sensors, inserted ipsilaterally in the parieto-temporal and the occipital lobes. Two levels of rotational acceleration were used in the experiments; one higher, corresponding to the threshold limit for moderate diffuse brain injury, and one lower, close to being noninjurious. Several pressure recordings were performed in each rabbit at the two acceleration levels. The pressure recordings invariably revealed the same general characteristics of rapid, positive and negative pressures within the brain, with variations in amplitude and duration, lasting for up to 10 ms. A major finding was the generation of powerful negative pressures, as low as 0.3 bars in absolute pressure. The most prominent difference in amplitudes of the negative peak pressures between the two applied acceleration levels was demonstrated at the parieto-temporal location. The presented pressure recordings are the first to disclose the generation of transient, powerful intracerebral pressures at rotational acceleration of the head, which must be considered in studies of brain injury generation and distribution as well as prevention.