Phosphate metabolites and steroid hormone receptors of benign and malignant breast tumors. A Nuclear Magnetic Resonance study

Phosphorous 31 (31P) nuclear magnetic resonance (NMR) spectra were recorded from perchloric acid extracts of benign and malignant breast tumors. The spectra were correlated with the histopathologic diagnosis and the steroid receptor status of the tumor. Higher relative content of the lipid-derived metabolite glycerolphosphoethanolamine (GPE), the high-energy nucleoside phosphates (nucleoside-diphosphate [NDP], nucleoside-triphosphate [NTP]), and sugar esters of uridine diphosphate (UDPS) appeared in the carcinomas. Malignant tumors also showed a lower ratio of phosphoethanolamine to phosphocholine (PE/PC) than benign conditions. Lower content of the lipid-derived metabolite glycerolphosphocholine (GPC) and high content of the high-energy compound phosphocreatine (PCr) were associated with malignant tumors having high content of estrogen receptors (ER). High PCr content was also associated in the carcinomas with high progesterone receptors (PgR) content. In the benign tumors NDP and NTP were higher in tumors with high PgR content. The authors suggest that 31P magnetic resonance spectroscopy (MRS) of the breast can provide additional variables to diagnose malignancy, and when combined with magnetic resonance imaging (MRI), invasive procedures may be avoided. It also seems that levels of PCr and GPC obtained from the spectra can serve as markers to hormonal receptor status of breast carcinomas, and may be used in addition to the ER and PgR content to improve prediction of the response to hormonal therapy. Additional development requires in situ MRI and MRS combined studies.     

Efficacy and toxicity of amiodarone for the treatment of supraventricular tachyarrhythmias

Amiodarone is an effective agent for all types of supraventricular tachyarrhythmias regardless of mechanism and may, in fact, control a high percentage of supraventricular tachyarrhythmias refractory to conventional antiarrhythmic agents. However, its toxicity should temper enthusiasm for the use of the medication in non-life-threatening arrhythmias. As always, when recommending specific therapies the potential benefit should be weighed in light of the related risk. In patients with life disordering, drug-refractory atrial fibrillation, it seems reasonable to attempt control with amiodarone. Likewise in patients with ectopic atrial tachycardias refractory to conventional agents, this seems reasonable as well. Other and better therapies are available for patients with life-threatening arrhythmias associated with the Wolff-Parkinson-White syndrome. While amiodarone is moderately effective in these patients, the advent of improved surgical techniques and the relatively low risk of an operation make surgery the treatment of choice. The role of IV amiodarone, acutely, in the treatment of supraventricular tachyarrhythmias remains to be defined.     

Lithium for irritability in Post-Traumatic stress disorder

Irritability is often a problem for patients with Post-Traumatic Stress Disorder (PTSD). We describe two cases that illustrate the use of lithium in the treatment of veterans with PTSD who complained of serious problems with irritability or angry outbursts. These cases are discussed in the context of evidence that lithium may be useful in other patients with disorders of impulse control. The evidence linking disorders of anger and impulse control to a dysregulation in neurotransmitter regulation, particularly in serotonergic pathways, supports a psychopharmacologic approach to treatment. These findings should lead to further study of the role of lithium in the treatment of this symptom complex in patients with PTSD.     

High-Temperature Short-Time Heat Inactivation of HIV and Other Viruses in Human Blood Plasma

An ultra-short-time heating system was used to process blood plasma spiked with various viruses (HIV, vesicular stomatitis virus, encephalomyocarditis virus). Virus reduction and recovery of plasma proteins were measured at various temperatures from 65 to 85 degrees C. Processing at 77 degrees C and 0.006 s resulted in a high level of virus kill, including greater than or equal to 4.4 log10 HIV, while maintaining protein structure and activity essentially intact.     

Recombinant α2(IV)NC1 domain of type IV collagen is an effective regulator of retinal capillary endothelial cell proliferation and inhibits pre-retinal neovascularisation

Background A recombinant form of the α2(IV)NC1 domain of type IV collagen has been shown to have potent anti-angiogenic activity although this peptide has not been studied in the context of proliferative retinopathies. In the current investigation we examined the potential for α2(IV)NC1 to regulate retinal microvascular endothelial cell function using a range of in vitro and in vivo assay systems. Materials and methods α2(IV)NC1 at concentrations between 0.1 and 1 μg/ml was added to retinal microvascular endothelial cells (RMECs) followed by assessment of cell attachment, proliferation and survival. This agent was also tested within a novel in vitro three-dimensional retinal angiogenesis assay and the number of angiogenic sprouts quantified. α2(IV)NC1 was also delivered intra-vitreally to mice with oxygen-induced proliferative retinopathy (OIR) and neovascularisation evaluated in comparison with vehicle-treated controls. Results RMECs treated with α2(IV)NC1 (0.1, 0.5 and 1 μg/ml) showed delayed attachment at 3 h post-seeding, although this deficit had been restored at the 6-h time point. BrdU assay of DNA replication revealed that confluent RMECs treated with α2(IV)NC1 showed no measurable response in comparison with vehicle-treated controls. By contrast, proliferation of sub-confluent RMECs was significantly reduced by α2(IV)NC1 at 0.5 μg/ml (P<0.01). α2(IV)NC1 also induced apoptosis in RMECs and inhibited angiogenesis of pre-existing retinal vascular networks in vitro (P<0.001). Intra-vitreal injection of α2(IV)NC1 in the OIR model significantly inhibited pre-retinal neovascularisation compared with vehicle-treated controls (P<0.001). Conclusion α2(IV)NC1 inhibits angiogenesis in the retinal microvasculature. This recombinant protein has potential for the treatment of neovascularisation in proliferative retinopathies. BioStratum Inc. did not sponsor this research in any way. None of the authors are paid consultants with this company.     

Biological Markers of Breast Cancer: A Review

This review of biological markers of breast carcinoma has summarized a fairly representative series of studies pertaining to endocrine, carcinoembryonic, tissue-associated, serologic, biochemical, and specific tumor markers, with attention to some of the contributions from genetic engineering techniques applied to this research area. It is meant to be a helpful review with two purposes: those involved in research or clinical studies of breast cancer may wish to use this review as a basis for adding additional references in each category and to refer to the references provided for further study, thought, and synthesis of the data, perhaps to stimulate new Associations between pertinent facts; those involved in the general scientific or clinical fields may wish to use it as an overview of biological markers pertaining to a particular form of cancer and perhaps this review will permit faster, more easily asscessible synthesis of data, and a better understanding of a variety of parameters which are Associated with breast cancer diseases.