Control of maximum sarcoplasmic reticulum Ca load in intact ferret ventricular myocytes. Effects Of thapsigargin and isoproterenol

Functional neuroanatomical correlates subserving maintenance rehearsal relative to a reading control task were investigated with positron emission tomography imaging of cerebral blood flow in 6 healthy older participants and 6 patients with mild Alzheimer's disease (AD). Rehearsal and reading rates and number of unique words rehearsed did not differ significantly for the 2 groups. The right dorsolateral prefrontal cortex was activated in both groups during rehearsal, highlighting this region's role in short-term maintenance of verbal information. A shift in cortical processing resources to more anterior brain regions with increased rehearsal list length was seen, likely reflecting greater demands on frontal cortex as cognitive load grows. Whereas controls showed unilateral right frontal activation during rehearsal, AD patients demonstrated bilateral frontal activation, possibly reflecting compensatory recruitment of neural resources.     

Risk factors and clinical outcomes between fungal and bacterial keratitis: a comparative study

OBJECTIVE: Thirty years ago, cardiopulmonary resuscitation (CPR) was primarily developed for otherwise healthy individuals who experienced sudden cardiac arrest. Today, CPR is widely viewed as an emergency procedure that can be attempted on any person who undergoes a cessation of cardiorespiratory function. Therefore, the appropriateness of CPR has been questioned as a matter of the outcome, the patient's preferences, and the cost. The objective of this article is to analyse ethical issues in prehospital resuscitation. ARGUMENTS: CPR is bound by moral considerations that surround the use of any medical treatment. According to Beauchamp and Childress, the hierarchy of justification in biomedical ethics consists of ethical theories, principles, rules, and particular judgements and actions. The decision to start CPR is based on the medical judgement that a person is suffering from circulatory arrest. The decision is justified by the moral rule that the victim of a cardiac arrest has the right to survive and to receive CPR. Moral rules are more specific to contexts and are based on ethical principles. The principle of beneficence means the provision of benefits for the promotion of welfare. Talking about beneficence in resuscitation means once again reporting stories of success, as many victims of pre- and in-hospital sudden death have been saved in the past. Nevertheless, resuscitative efforts still remain unsuccessful in the majority of cases, involving the principle of nonmaleficence. There is potential harm in CPR. Survivors may recover cardiac function, but sustain severe hypoxic brain damage, at worst surviving without awakening for months or years. In particular, post-traumatic CPR is associated with an extremely poor outcome, leading to the issue of futility. However, futility should be defined in a strict fashion, as there might be an individual chance of survival. The principle of respect for autonomy means the right of a patient to accept or reject medical treatment, which continues in emergency conditions and after the patient has lost consciousness. The time frame in CPR requires medical decision-making within seconds, and CPR is usually initiated without the patient's involvement. If the patient's wish's can be ascertained later on, life-sustaining therapies might be withdrawn at the time. Terminally ill but still competent patients should be encouraged to write a no-CPR document, which does not deny patients relief from severe symptoms, but might facilitate withholding resuscitative efforts at the scene. The principle of justice affects priorities in the allocation of health care resources. The decision made for a particular patient might delay or prevent emergency treatment in other patients who could receive greater benefit. CONCLUSIONS: The standard of care remains the prompt initiation of CPR. However, ethical principles such as beneficence, nonmaleficence, autonomy, and justice have to be applied in the unique setting of emergency medicine. Physicians have to consider the therapeutic efficacy of CPR, the potential risks, and the patient's preferences.     

Modulation of the enzymatic properties of protein phosphatase 2A catalytic subunit by the recombinant 65-kDa regulatory subunit PR65alpha

In situ estrogen synthesis by hormone-dependent breast cancers could potentially regulate cellular proliferation through autocrine or paracrine mechanisms. Several biochemical studies have demonstrated activity of the enzyme aromatase, the rate-limiting step for estrogen synthesis, in breast tumor homogenates. Prior immunohistochemical studies in breast neoplasms demonstrated aromatase antibody binding to both stroma and parenchyma, but biochemically measured enzyme activity significantly correlated only with the level of staining in the stromal component. The present study sought to provide more direct evidence of the predominant role for stromal cell aromatase in breast tumor tissue. Accordingly, breast tumor stromal and epithelial cells were examined for aromatase enzyme activity and messenger ribonucleic acid (mRNA) expression. Stromal and epithelial cells from benign tissue served as a means of comparing activity and regulation in benign and tumor tissue. Enzyme activity in stromal cells from breast tumor tissue was low basally, but increased by 30- to 1200-fold when induced by dexamethasone. Combining dexamethasone with phorbol esters and cAMP produced an additional 1.2- to 4.1-fold stimulation. Analyses of exons III/V and exons IX/X demonstrated that aromatase mRNA expression was also substantially increased by these treatments. Increases in enzyme activity and mRNA expression in cells from benign breast stroma paralleled those observed in tumor stroma, although the increases in enzyme activity were generally lower. In contrast to the responses observed in stromal cells, epithelial cells from breast tumor or nonmalignant breast tissue were unresponsive to dexamethasone, either added alone or in combination with phorbol esters and cAMP. This study provides direct biochemical evidence that aromatase is present in stroma within breast tumors, as in surrounding tissues, and suggests that estrogen synthesis within the tumor may modulate tumor growth via a paracrine mechanism.     

Three-year follow-up of a posttraumatic right coronary aneurysm

Posttraumatic saccular aneurysm of the right coronary artery is a rare complication of nonpenetrating chest trauma. We observed a posttraumatic coronary aneurysm for 3 years and noted that the aneurysm has changed in shape, with partial obliteration of the aneurysm sac, and that its clinical course was uneventful with conservative treatment. Surgical removal of aneurysms has been advocated in the literature; however, conservative medical treatment and a wait-and-see policy can be considered as a treatment modality for posttraumatic coronary aneurysm.     

Effects of keratinocyte and hepatocyte growth factor in vivo: implications for retrovirus-mediated gene transfer to liver

We have previously shown that intravenous administration of keratinocyte growth factor (KGF) induces hepatocyte proliferation, allowing for efficient and noninvasive in vivo gene transfer with high-titer retroviral vectors in mice. The distinctive periportal distribution of transduced cells led us to investigate the ability of virus-sized particles to perfuse the liver adequately after growth factor treatment. We found that perfusion was adequate, and that transduction was limited to the periportal region because only those cells were stimulated to divide. Cells in this region also showed increased expression of Ram-1, the receptor for the murine Moloney leukemia virus (MoMLV) amphotropic envelope, after KGF treatment. In further studies we found that recombinant hepatocyte growth factor (HGF) induces a different population of hepatocytes to divide and upregulate Ram-1. The differential pattern of induction suggested that combining KGF and HGF would improve gene transfer efficiency further. Indeed, simultaneous delivery of both growth factors leads to an overall increase in the number of proliferating cells. Importantly, when coupled with MoMLV delivery, efficiency of gene transfer increased. These results confirm the utility of growth factors for noninvasive hepatic gene transfer in mice, and demonstrate how experiments to define the mechanism of transduction can be taken advantage of to develop improved gene transfer protocols.     

Recombinant PML adenovirus suppresses growth and tumorigenicity of human breast cancer cells by inducing G1 cell cycle arrest and apoptosis

Our previous studies demonstrated that the promyelocytic leukemia gene, PML which involved in the 15;17 translocation in acute promyelocytic leukemia (APL) is a growth and transformation suppressor. In this study, recombinant PML adenovirus, Ad-PML was constructed and used to infect human breast cancer cells in vitro and in vivo, the anti-oncogenic function of PML and its mechanism of growth suppressing effect in breast cancer cells were examined. We showed that Ad-PML effectively infected the MCF-7 and SK-BR-3 cells. A high level of PML protein was expressed within 24 h post-infection and a detectable level remained at day 16. Ad-PML significantly suppressed the growth rate, clonogenicity, and tumorigenicity of breast cancer cells. Intratumoral injections of MCF-7-induced tumors by high titer Ad-PML suppressed tumor growth in nude mice by about 80%. The injection sites expressed high level of PML and associated with a massive apoptotic cell death. To elucidate the molecular mechanism of PML's growth suppressing function, we examined the effect of Ad-PML on cell cycle distribution in MCF-7 and SK-BR-3 cells. We found that Ad-PML infection caused a cell cycle arrest at the G1 phase. We further showed that G1 arrest of MCF-7 cells is associated with a significant decrease in cyclin D1 and CDK2. An increased expression of p53, p21 and cyclin E was found. The Rb protein became predominantly hypophosphorylated 48 h post-infection. These findings indicate that PML exerts its growth suppressing effects by modulating several key G1 regulatory proteins. Our study provides important insight into the mechanism of tumor suppressing function of PML and suggests a potential application of Ad-PML in human cancer gene therapy.     

Compression of the upper cervical spinal cord causing symptoms of brainstem compromise. A case report

STUDY DESIGN: A case is reported in which a flexion-induced compression of the upper cervical spinal cord caused symptoms of brainstem compromise in the absence of radiographic evidence of osseous instability. OBJECTIVES: A 41-year-old woman developed postoperative cervical instability with flexion-induced neurologic symptoms referable to the brainstem. The instability was caused by direct compression at the third cervical vertebral body, which in turn was caused by differential movements between the neuraxis and skeletal elements in the upper cervical spine. SUMMARY OF BACKGROUND DATA: Pathologic processes at the craniocervical junction may cause brainstem compromise with neurologic symptoms. The mechanism of brainstem involvement is usually either vertebrobasilar insufficiency or direct mechanical compression. In cases where the brainstem is compressed by skeletal elements, the compressing osseous structures usually are the walls of the foramen magnum or the odontoid process, or, less frequently, the atlas or axis vertebrae. Symptoms of brainstem dysfunction caused by dynamic compression at the level of the third cervical vertebra in the absence of hindbrain herniation are unusual and, to the best of the authors' knowledge, have not been described previously. METHODS: The patient underwent initial examination, evaluation, and periodic follow-up examination with magnetic resonance imaging from the time of her first visit until 26 months after the surgical treatment. The patient experienced postsurgical instability with dynamic compression by the C3 vertebral body, which caused brainstem compromise. Surgical treatment consisted of decompressive C3 corpectomy and fusion of C2 to C6, supplemented by anterior fixation. RESULTS: After undergoing surgical decompression of C3, reconstruction, and anterior internal fixation of C2 to C6, the patient had dramatic neurologic improvement. Diplopia, paresthesia, and nystagmus disappeared immediately after surgery. Swallowing difficulties, hoarseness, and vertigo improved gradually. At follow-up examination 26 months after surgery, the patient was asymptomatic. Magnetic resonance imaging showed good position of the construct, with no evidence of compression of the spinal cord or brainstem. CONCLUSIONS: Instability of the cervical spine may result in symptoms of brainstem dysfunction, even in the absence of hindbrain herniation. This instability is explained by the differential movement between the bony structures and neuraxis in the upper cervical region. Diagnosis and adequate management of this instability alleviates the neurologic symptoms and prevents possible hazardous complications.     

Colchicine activates actin polymerization by microtubule depolymerization

Dog exposure to doses from 39 to 124 Gy results in an increase of heart rate and tension in control of the cardiac rhythm, the extent being dose dependent. An additional physical load on the cardiovascular animals system reveals a high functional control reserves of the cardiovascular system which provides stable functioning even after exposure to the above doses.     

Diabetic cardiomyopathy

BACKGROUND: A rising percentage of tetracycline-resistant Propionibacterium acnes strains has been reported in the English literature. PATIENTS AND METHODS: We studied a population of 16 patients with acne who had been treated with oral tetracyclines during the preceding year. A bacteriological examination of a skin biopsy was obtained in all patients to determine aerobic and anaerobic flora as wells as resistance to tetracycline and minocycline. RESULTS: Staphylococcus epidermidis strains were frequently resistant to tetracycline (87.5%) as well as minocycline (30%). Tetracycline-resistant Propionibacterium acnes were also observed (7%). Inversely, we were unable to evidence any minocycline-resistant Propionibacterium acnes strains. CONCLUSION: These findings emphasize the importance of determining whether therapeutic response is related or not to the presence of resistant strains.     

The diagnostic accuracy of cervico-vaginal fetal fibronectin in predicting preterm delivery: an overview

OBJECTIVE: To determine the accuracy with which cervico-vaginal fetal fibronectin predicts preterm delivery using systematic quantitative overview of the available literature. DESIGN: Online searching of MEDLINE database (1966 to April 1996), scanning of bibliography of known primary and review articles and review of recent journal issues. Study selection, assessment of study quality and data extraction were performed in duplicate under masked conditions. Likelihood ratios were generated in subgroups of symptomatic and asymptomatic pregnant women by pooling data from different studies. An LR of > 10 or < 0.1 indicated conclusive changes in the pretest probability of preterm delivery while an LR of 5-10 or 0.2-0.1 indicated only moderate changes. PARTICIPANTS: Seven hundred and twenty-three symptomatic women with threatened preterm labour included in nine studies and 847 asymptomatic women (635 low risk and 212 high risk) included in six studies selected for meta-analyses. MAIN OUTCOME MEASURES: Likelihood ratios for positive and negative test results using delivery at < 37 and < 34 weeks of gestation, and within one week of testing as outcome measures. RESULTS: In symptomatic women a positive test predicted delivery < 37 weeks of gestation with a pooled likelihood ratio (LR) of 4.6 (95% CI 3.5-6.1) while a negative test had a pooled LR of 0.5 (95% CI 0.4-0.6). For delivery < 34 weeks of gestation, the pooled LR was 2.6 (95% CI 1.8-3.7) for a positive test and 0.2 (95% CI 0.1-0.5) for a negative test. For delivery within one week of testing, the pooled LR was 5.0 (95% CI 3.8-6.4) for a positive test and 0.2 (95% CI 0.1-0.4) for a negative test. In asymptomatic women at low risk of delivery < 37 weeks of gestation the pooled LR was 3.2 (95% CI 2.2-4.8) for a positive test and 0.8 (95% CI 0.7-0.9) for a negative test. In high risk asymptomatic women using delivery < 37 weeks of gestation as an outcome measure the pooled LR was 2.0 (95% CI 1.5-2.6) for a positive test and 0.4 (95% CI 0.2-0.8) for a negative test. For delivery < 34 weeks of gestation in high risk, asymptomatic women the pooled LR was 2.4 (95% CI 1.8-3.2) for a positive test and 0.6 (95% CI 0.4-0.9) for a negative test. CONCLUSION: The presence of fetal fibronectin in cervico-vaginal mucus has limited accuracy in predicting preterm delivery as the likelihood ratios for positive and negative test results generated only minimal to moderate changes in the pretest probability of preterm birth.