Mammographic density and breast cancer after ductal carcinoma in situ
Habel LA, Dignam JJ, Land SR et al. JNCI 2004;96(19):1467-72.
Women with ductal carcinoma in situ (DCIS) are at substantially increased risk for a second breast cancer, but few strong predictors for these subsequent tumors have been identified. We used Cox regression modeling to examine the association between mammographic density at diagnosis of DCIS of 504 women from the National Surgical Adjuvant Breast and Bowel Project B-17 trial and risk of subsequent breast cancer events. In this group of patients, mostly 50 years old or older, approximately 6.6% had breasts categorized as highly dense (i.e., =75% of the breast occupied by dense tissue). After adjusting for treatment with radiotherapy, age, and body mass index, women with highly dense breasts had 2.8 (95% confidence interval [CI] = 1.3 to 6.1) times the risk of subsequent breast cancer (DCIS or invasive), 3.2 (95% CI = 1.2 to 8.5) times the risk of invasive breast cancer, and 3.0 (95% CI = 1.2 to 7.5) times the risk of any ipsilateral breast cancer, compared with women with less than 25% of the breast occupied by dense tissue. Our results provide initial evidence that the risk of second breast cancers may be increased among DCIS patients with highly dense breasts.

The ubiquitin-mediated protein degradation pathway in cancer: therapeutic implications
Burger AM, Seth AK. Eur J Cancer 2004;40(15):2217-29.
The highly conserved eukaryotic ubiquitin-proteasome system (UP-S) plays a pivotal role in protein homeostasis and is critical in regulating normal and cancer-related cellular processes. The hierarchical nature of the UP-S provides a rich source of molecular targets for specific intervention and has therefore arisen as a promising approach to innovative anticancer therapies. The first in class proteasome inhibitory agent Bortezomib (Velcade) has recently obtained regulatory approval for the treatment of multiple myeloma. Ubiquitin-mediated degradation is a complex process that is comprised of well defined steps involving ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s). Although a single E1 activates the ubiquitin conjugation machinery, a large number of E2 conjugating enzymes and E3 ligases are now known to exist. Proteins tagged with ubiquitin are subsequently recognised by the proteasome for digestion and fragmentation. The enzymatic nature, multitude of E3s and their specific substrate recognition predestines them as therapeutic targets. This article will review known inhibitors of the proteasome and their molecular mechanisms as well as ongoing developments and promising avenues for targeting substrate-specific E3 ligases that are likely to yield a new class of therapeutics that will serve and complement the armamentarium of anticancer drugs.

The interplay between Src and integrins in normal and tumor biology
Playford MP, Schaller MD. Oncogene 2004;23(48):7928-46.
Src family nonreceptor protein tyrosine kinases transduce signals that control normal cellular processes such as cell proliferation, adhesion and motility. Normally, cellular Src is held in an inactive state, but in several cancer types, abnormal events lead to elevated kinase activity of the protein and cause pleiotropic cellular responses inducing transformation and metastasis. A prerequisite of the ability of a cancer cell to undergo metastasis into distant tissues is to penetrate surrounding extracellular matrices. These processes are facilitated by the integrin family of cell adhesion molecules. As is the case with Src, altered integrin activity or substrate affinity can contribute to the neoplastic phenotype. Therefore, understanding the interplay between Src and integrin function has been of intense interest over the past few years. This review focuses on the role of Src and integrin signaling in normal cells and how this is deregulated in human cancer. We will identify the key players in the integrin-mediated signaling pathways involved in cell motility and apoptosis, such as FAK, paxillin and p130(CAS), and discuss how Src signaling affects the formation of focal adhesions and the extracellular matrix. FAK, paxillin and p130(CAS), and discuss how Src signaling affects the formation of focal adhesions and the extracellular matrix.

Press Release: The 2004 Nobel Prize in Physiology or Medicine
Source: www.nobelprize.org
The Nobel Assembly at Karolinska Institutet has today decided to award The Nobel Prize in Physiology or Medicine for 2004 jointly to Richard Axel and Linda B. Buck for their discoveries of "odorant receptors and the organization of the olfactory system" (4 October 2004)
Summary. The sense of smell long remained the most enigmatic of our senses. The basic principles for recognizing and remembering about 10,000 different odours were not understood. This year's Nobel Laureates in Physiology or Medicine have solved this problem and in a series of pioneering studies clarified how our olfactory system works. They discovered a large gene family, comprised of some 1,000 different genes (three per cent of our genes) that give rise to an equivalent number of olfactory receptor types. These receptors are located on the olfactory receptor cells, which occupy a small area in the upper part of the nasal epithelium and detect the inhaled odorant molecules. Each olfactory receptor cell possesses only one type of odorant receptor, and each receptor can detect a limited number of odorant substances. Our olfactory receptor cells are therefore highly specialized for a few odours. The cells send thin nerve processes directly to distinct micro domains, glomeruli, in the olfactory bulb, the primary olfactory area of the brain. Receptor cells carrying the same type of receptor send their nerve processes to the same glomerulus. From these micro domains in the olfactory bulb the information is relayed further to other parts of the brain, where the information from several olfactory receptors is combined, forming a pattern. Therefore, we can consciously experience the smell of a lilac flower in the spring and recall this olfactory memory at other times.
Richard Axel, New York, USA, and Linda Buck, Seattle, USA, published the fundamental paper jointly in 1991, in which they described the very large family of about one thousand genes for odorant receptors. Axel and Buck have since worked independent of each other, and they have in several elegant, often parallel, studies clarified the olfactory system, from the molecular level to the organization of the cells.
The olfactory system is important for life quality. When something tastes really good it is primarily activation of the olfactory system which helps us detect the qualities we regard as positive. A good wine or a sunripe wild strawberry activates a whole array of odorant receptors, helping us to perceive the different odorant molecules. A unique odour can trigger distinct memories from our childhood or from emotional moments - positive or negative - later in life. A single clam that is not fresh and will cause malaise can leave a memory that stays with us for years, and prevent us from ingesting any dish, however delicious, with clams in it. To lose the sense of smell is a serious handicap - we no longer perceive the different qualities of food and we cannot detect warning signals, for example smoke from a fire. Olfaction is of central importance for most species. All living organisms can detect and identify chemical substances in their environment. It is obviously of great survival value to be able to identify suitable food and to avoid putrid or unfit foodstuff. Whereas fish has a relatively small number of odorant receptors, about one hundred, mice - the species Axel and Buck studied - have about one thousand. Humans have a somewhat smaller number than mice; some of the genes have been lost during evolution.
Smell is absolutely essential for a newborn mammalian pup to find the teats of its mother and obtain milk - without olfaction the pup does not survive unaided. Olfaction is also of paramount importance for many adult animals, since they observe and interpret their environment largely by sensing smell. For example, the area of the olfactory epithelium in dogs is some forty times larger than in humans.
A large family of odorant receptors. The olfactory system is the first of our sensory systems that has been deciphered primarily using molecular techniques. Axel and Buck showed that three per cent of our genes are used to code for the different odorant receptors on the membrane of the olfactory receptor cells. When an odorant receptor is activated by an odorous substance, an electric signal is triggered in the olfactory receptor cell and sent to the brain via nerve processes. Each odorant receptor first activates a G protein, to which it is coupled. The G protein in turn stimulates the formation of cAMP (cyclic AMP). This messenger molecule activates ion channels, which are opened and the cell is activated. Axel and Buck showed that the large family of odorant receptors belongs to the G protein-coupled receptors (GPCR).
All the odorant receptors are related proteins but differ in certain details, explaining why they are triggered by different odorous molecules. Each receptor consists of a chain of amino acids that is anchored into the cell membrane and traverses it seven times. The chain creates a binding pocket where the odorant can attach. When that happens, the shape of the receptor protein is altered, leading to G protein activation.
One type of odorant receptor in each olfactory receptor cell. Independently, Axel and Buck showed that every single olfactory receptor cell expresses one and only one of the odorant receptor genes. Thus, there are as many types of olfactory receptor cells as there are odorant receptors. It was possible to show, by registering the electrical signals coming from single olfactory receptor cells, that each cell does not react only to one odorous substance, but to several related molecules - albeit with varying intensity. Buck's research group examined the sensitivity of individual olfactory receptor cells to specific odorants. By means of a pipette, they emptied the contents of each cell and showed exactly which odorant receptor gene was expressed in that cell. In this way, they could correlate the response to a specific odorant with the particular type of receptor carried by that cell.
Most odours are composed of multiple odorant molecules, and each odorant molecule activates several odorant receptors. This leads to a combinatorial code forming an "odorant pattern" - somewhat like the colours in a patchwork quilt or in a mosaic. This is the basis for our ability to recognize and form memories of approximately 10,000 different odours. Olfactory receptor cells activate micro regions in the olfactory bulb. The finding that each olfactory receptor cell only expresses one single odorant receptor gene was highly unexpected. Axel and Buck continued by determining the organization of the first relay station in the brain. The olfactory receptor cell sends its nerve processes to the olfactory bulb, where there are some 2,000 well-defined microregions, glomeruli. There are thus about twice as many glomeruli as the types of olfactory receptor cells.
Axel and Buck independently showed that receptor cells carrying the same type of receptor converge their processes into the same glomerulus, and Axel's research group used sophisticated genetic technology to demonstrate in mice the role of the receptor in this process. The convergence of information from cells with the same receptor into the same glomerulus demonstrated that also glomeruli exhibit remarkable specificity (see figure).

In the glomeruli we find not only the nerve processes from the olfactory receptor cells but also their contacts with the next level of nerve cells, the mitral cells. Each mitral cell is activated only by one glomerulus, and the specificity in the information flow is thereby maintained. Via long nerve processes, the mitral cells send the information to several parts of the brain. Buck showed that these nerve signals in turn reach defined micro regions in the brain cortex. Here the information from several types of odorant receptors is combined into a pattern characteristic for each odour. This is interpreted and leads to the conscious experience of a recognizable odour.
Pheromones and taste. The general principles that Axel and Buck discovered for the olfactory system appears to apply also to other sensory systems. Pheromones are molecules that can influence different social behaviours, especially in animals. Axel and Buck, independent of each other, discovered that pheromones are detected by two other families of GPCR, localized to a different part of the nasal epithelium. The taste buds of the tongue have yet another family of GPCR, which is associated with the sense of taste.
REFERENCE. Buck L, Axel R. Cell 1991;65:175-87.

European bodies reach an uneasy truce on embryonic stem-cell research
Schairer C, Mink PJ, Carroll L et al. JNCI 2004;96(17):1311-21.
On September 30 in Brussels, after a bitter dispute with the European Parliament over research involving the use of human embryonic stem cells, the European Union (EU) Council of Science Ministers eventually approved the Sixth Framework Research Programme. But the approval, which will allow the 5-year, 17.5 billion Euro programme to launch officially in early November, unexpectedly included a 1-year moratorium on stem- cell research funding. The Council - the central decision-making body of the EU - and the Parliament had reached an unwritten agreement in June over the approval of the Framework Programme, which allowed EU funding of stem-cell research in countries where it was not prohibited (Lancet 2001; 358: 1972). However, the Council adopted a unilateral decision in late July - under the Danish presidency of the EU - to embargo such financing until the end of 2003. The Parliament protested the Council's decision on grounds that it was not a consensus agreement and the moratorium did not have par- liamentary approval. Several members of the Parliament's Committee on Industry, External Trade, Research and Energy, headed by socialist Carlos Westendorp, threatened that, if the moratorium went forward without consultation, Parliament could block the programme's entire budget - or even sue the Council via the EU Court of Justice. The Committee went as far as querying the constitutional legality of the Council decision. The threat prompted representatives from the two parts to negotiate again and to reach an agreement. This stipulates that "further provisions on the funding of research activities involving the use of human embryos and human embryonic stem cells will be established before the end of 2003, on the basis of a new proposal (based on an in-depth ethical, technical, and political study) from the European Commission and in consultation with the European Parliament". Until then, says the statement Commission "will not propose to finance such research projects, unless they involve (already established) banked or isolated human embryonic stem cells in culture". The new commitment also stipulates that "proposals for [funding] research projects involving (human embryonic stem cells) will be submitted to a regulatory committee (where al EU countries will be represented)". Commenting on this latest compromise, which Italy was the only country to oppose, Westendorp noted: "What we`ve learned from all this is that any future agreement with the Council must be confirmed in writing."
. News. Ann Oncol 2002; 13:1694.
2. Brenner DE. New concepts in combination oncological thera- peutics. Ann Oncol 2002:13:1698.
3. Gollub MJ. Virtual colonoscopy. Lancet 2002;360:964.
4. Bosch H. European bodies reach an uneasy truce. Lancet 2002; 360:1080.

General Information: yagi@imap.pitt.edu
Our Mission
CONTENT OF "CLINICAL GUIDELINES FOR TELEPATHOLOGY"
1 Introduction
2 Scope
3 The Practice of Telepathology: Responsibilities of the Pathologist
3.1 Primary Diagnosis Telepathology
3.1.1. Technicians, Technologists and Pathologist's Assistants in Primary Diagnosis Telepathology
3.2. Second Opinion Telepathology
3.2.1. Responsibilities of the Referring Pathologist
3.2.2. Responsibilities of the Consulting Pathologist
4 Training and Quality Control
4.1 Training of Pathologists
4.2 Training of Technicians, Technologists and Pathologist's Assistants
4.3 Quality Control
5 Documentation and Archiving
6 Data Integrity and Security
A Draft Version 2.4; May 20, 1999; The American Telemedicine Association
1 Introduction
This is a working draft of clinical guidelines for telepathology written with the expectation that others will rewrite it and add to it. To keep this document generally applicable it steers clear of technical specifications or implementation issues and concentrates on the responsibilities of the pathologist in telepathology.
2 Scope
For the purpose of this document, Telepathology will be defined as electronic, multimedia communication between pathologists for the purpose of primary diagnoses and diagnostic consultation second opinion. It may also be extended to include similar diagnostic communication between other physicians (non-pathologists) and a laboratory staff by qualified laboratory personnel - trained technicians, technologists, or a pathologist's assistants - and a remote pathologist and when the laboratory personnel is under the supervision of a pathologist.
The concepts discussed in this document should be generally applicable to all three types of telepathology; static (store and forward), dynamic (synchronous), and hybrid (static-dynamic) implementations.
3 The Practice of Telepathology: Responsibilities of the Pathologist
Pathologists have been sending each other cases for diagnostic second opinion for many years. This collaboration has traditionally involved the sending of stained slides, unstained slides, tissue blocks, wet tissue, pathology reports and cover letters via courier or through conventional mail. The system has worked well, and is the "gold standard" by which diagnoses are compared between institutions. In defining guidelines for second opinion telepathology, pathologists should borrow, whenever possible, from the workflows and responsibilities set up in the courier based system.
Guidelines for primary opinion telepathology should be driven from best practices in conventional laboratory procedures. It is understood that pathologists often work in central offices geographically separated from both the clinics (where cytology and surgical samples are obtained) and the histology laboratories (where cytology preparations and tissue are processed and slides are made).
Sections 3.1 and 3.2 detail proposed responsibilities of pathologists and laboratory personnel in both primary diagnosis telepathology (section 3.1) and second opinion telepathology (section 3.2). Though the discussion is framed in a telepathology environment involving multiple institutions, the responsibilities are similar if telepathology occurs within a single institution.
3.1 Primary Diagnosis Telepathology
In telepathology, specimens at a referring site are diagnosed by pathologists at a remote site. In primary diagnosis telepathology, the diagnostic effort and responsibility resides entirely with the pathologist at the remote site. The medical responsibilities for a site initiating a telepathology session for primary diagnosis, are similar to those of a laboratory sending glass slides by courier or conventional mail to another pathologist for primary diagnosis in a traditional environment. These include:
1. The laboratory must identify the case appropriately. Traditionally this has meant, at a minimum, local accession number and the patient's name as well as some indication of what material has been sent (the number or slides, blocks, reports, etc.) In the telepathology environment this must be extended to the appropriate documentation of images and information sent.
2. The laboratory must insure that all appropriate clinical information is conveyed to the remote pathologist. Traditionally this has usually meant an appropriately filled out requisition and/or the surgeon's operative report, however it can include additional information (for example, X-rays in bone pathology cases) or direct access to the clinicians involved depending on the situation and pathologists medical judgement. If, in the judgement of the pathologists involved, the system cannot provide adequate clinical information to the remote pathologist, telepathology should not be used to render a diagnosis or telepathology should be supplemented by other mechanisms.
3. The laboratory must insure that the remote pathologist has adequate access to appropriate diagnostic material. In a practice setting in which primary telepathology diagnoses are rendered, and a pathologist is not present at a referring site, a methodology must be employed which insure that video sampling of gross tissues and glass slides is inclusive.
4. In addition to the medical responsibilities discussed above, the laboratory has responsibilities for data handling, archiving and security as discussed below.
3.1.1. Technicians, Technologists and Pathologist's Assistants in Primary Diagnosis Telepathology
Pathologist's Assistants, technologists and technicians have traditionally worked under the supervision of Pathologists in anatomic pathology laboratories. Appropriately trained personnel (pathologist's assistants, technologists and technicians) should be able to present cases and relevant materials, via telepathology, to other pathologists at remote sites.
1. Presenting Personnel should be adequately trained in the use of telepathology equipment and the limitations of telepathology
2. A pathologist should supervise the support personnel, and support personnel should have access to other pathologists throughout the telepathology session.
3.1.2. Responsibilities of the Pathologist in Primary Diagnosis Telepathology
In primary diagnosis telepathology, diagnostic effort and responsibility resides entirely with the pathologist at the remote site. If the remote pathologist supervises referring site, the pathologist takes on the roles and responsibilities of both referring and consulting pathologist in Section
3.2. Second Opinion Telepathology
In second opinion telepathology, diagnostic effort and responsibility resides with both the pathologists at the local site (referring pathologist) and the pathologist at the remote site (consulting pathologist).
3.2.1. Responsibilities of the Referring Pathologist
The medical responsibilities for a pathologist initiating a second opinion telepathology session are similar to those of a pathologist sending glass slides by courier to a consulting pathologist in a traditional environment. These include:
1. The referring pathologist must identify the case appropriately. Traditionally this has meant, at a minimum, local accession number and the patient's name as well as some indication of what material has been sent (the number or slides, blocks, reports, etc.) In the telepathology environment this must be extended to the appropriate labeling of images and documentation of the number of images sent.
2. The referring pathologist must insure that all appropriate clinical information is conveyed to the consulting pathologist. Traditionally for second opinion this has usually meant a cover letter and a copy of the referring pathologist's report, however it can include additional information (for example, X-rays in bone pathology cases) depending on the situation and the referring pathologist's medical judgement. If in the judgement of the referring pathologist, the telepathology system proposed for the consultation can not, adequately provide all of the appropriate clinical information to the consulting pathologist, telepathology should not be used for the consultation or telepathology should be supplemented by other mechanisms.
3. The referring pathologist must insure that the consulting pathologist has adequate access to appropriate diagnostic material. One of a pathologist's cardinal responsibilities is to appropriately sample specimens so as to arrive at the accurate diagnosis. The pathologists traditionally sub-sample gross specimens into blocks, and those blocks are then sub-sampled in the creation of slides. In traditional courier based consultations, it is not uncommon to have, on the judgement of the referring pathologist, only a subset of slides sent to the consulting pathologist. In some implementations of telepathology, a further level of sub sampling in which images representing selected fields from a slide are sent to the consulting pathologist. In these implementations, it is the responsibly of the referring pathologist to select these fields appropriately.
4. The referring pathologist must render a final report on a case. As in traditional pathology consultations, it is the responsibility of the referring pathologist, when receiving an opinion from a consulting pathologist, to reconcile his or her understanding of the case - and any clinical or pathological information not available to the consulting pathologist - with the opinion of the consulting pathologist and then reach an appropriate diagnosis. This responsibility should also exist in consultations based on telepathology. The use of telepathology should not relieve the referring pathologist of the responsibly to render to a final report on a case.
5. In addition to the medical responsibilities discussed above, the referring pathologist has responsibilities for data handling, archiving and security as discussed below.
3.2.2. Responsibilities of the Consulting Pathologist
A pathologist receiving a case via telepathology has a number of medical responsibilities similar to those of a pathologist receiving a case via courier:
1. The consulting pathologist should insure that he/she has received all materials sent by the referring pathologist. This has traditionally been done, in the courier-based model, by comparing the material listed in the cover letter (or other documentation) to the material received.
2. The pathologist must insure that appropriate standard operating procedures are in place at the referring site to insure that all the clinical information or pathologic material (tissue, blocks, etc.) necessary to adequately examine a case is available. If in the judgement of the consulting pathologist, the telepathology system proposed can not provide the necessary information to the consulting pathologist, telepathology should not be used for the consultation or telepathology should be supplemented by other mechanisms. If clinical information deemed necessary by the consulting pathologist is not available by any mechanism, an unqualified opinion should not be rendered.
3. In the traditional courier-based consultation, it is the responsibility of the consulting pathologist to determine if the material sent by the referring pathologist is of adequate quality to render a diagnosis. For example, it has been up to the consulting pathologist to determine if the slides proffered were adequately cut and/or stained. The quality needed for a diagnosis depends directly on the skill of the consulting pathologist and the diagnostic question involved. Consistent with the traditional, courier-based practice, it is the responsibility of the consulting pathologist to determine if the image quality is adequate for diagnosis. If the consulting pathologist feels that image quality and/or video image sampling are not adequate, he/she should request that the glass slides and or blocks be sent for analysis. This is consistent with traditional, courier-based practice.
4. The consulting pathologist should transmit his/her opinion/diagnosis to the referring pathologist in a mutually agreed upon manner. Observations that could effect patient care in a time sensitive manner should be transmitted directly to the referring pathologist.
5. In addition to the medical responsibilities discussed above, the consulting pathologist has responsibilities for data handling, archiving and security as discussed below.
4 Training and Quality Control
4.1 Training of Pathologists
Because the effectiveness and accuracy of telepathology depends critically on the skill and judgement of the pathologist, both referring and consulting pathologists practicing telepathology should be trained in telepathology.
1. Training should occur on the individual systems that the pathologist uses.
2. Training should occur also in general telepathology/imaging principles and limitations. The implementation of this training is an issue that requires discussion and consensus. Possibilities could include general web-based seminars and tests supported by the ATA, CAP, USCAP, etc. followed by practical examinations provided be the same organizations. (The CAP has similar programs ongoing for standard glass slide pathology.)
4.2 Training of Technicians, Technologists and Pathologist's Assistants
In an environment in which a technologist, a technician, or a pathologist's assistant is supervised by a local or a remote pathologist, he/she should be trained specifically in telepathology techniques.
4.3 Quality Control
Pathologists providing consultation by telepathology should be required to have at least 10% of their cases re-examined by another pathologist, comparing the transmitted images to the microscopic slide and any discrepancies should be noted.
5 Documentation and Archiving
The telepathology interaction is a vital part of a patient's care and as such must be documented in the medical record. To this end:
1. A diagnostic consultation by telepathology shall generate a formal report by the consulting pathologist. This report shall become a permanent part of the patient medical record. It is recommended that all reports, letters, clinical information and possibly static (still) images transmitted from the referring site to the pathologist as part of the telepathology encounter should be archived at the consultant's institution. This practice is consistent with that applied to courier based consultations.
2. All reports, letters, clinical information and static (still) images involved in a diagnostic consultation by telepathology, as well as the consultant's report, shall be archived as part of the medical record at the referring institution. This practice is consistent with those applied to courier based consultations. (Because image archiving requires special equipment not available at all institutions, the referring institution may allow the consulting institution or a third party to archive telepathology information, as long as the archiving is done under the rules or the referring institution.)
3. The telepathology encounter, and the general opinion of the consulting pathologist, shall be documented in the final report of the referring pathologist. This practice is consistent with those applied to courier based consultations.
4. Dynamic, real time images generated during a telepathology session need not be archived. Static (still) images shall be archived at that same image quality, file size and format that was used in the telepathology encounter. Static (still) images should be archived for at least as long as the glass slides involved in the case.
For cases in which diagnoses are based exclusively by static images, the entire image file should be archived.
6 Data Integrity and Security
By its nature, the telepathology encounter involves transmission and storage of confidential patient information. Though it is understood that no security system is foolproof and that the specific security mechanisms needed will depend on the specific telepathology implementation, parties engaging in telepathology shall insure that the telepathology system provides reasonable privacy and confidentiality by security measures including:
1. Message Security: A telepathology shall occur over secure networks, or shall be adequately encrypted. It is the responsibility of the consulting laboratory to provide a secure station for receiving diagnostic reports. Verifiable digital signatures may be allowed.
2. System Authentication: When appropriate, the system should authenticate itself unambiguously to all users, for example, using a third party certificate and private key.
3. User Authentication: The referring pathologist, consulting pathologist and all other persons using the system (administrators, assistants, etc.) shall be adequately authenticated to each other and to the system. This authentication should involve, at a minimum, a user name and password.
4. Activity Logs: All accesses to the system shall be logged by user and by case. The logs shall be reviewed on a regular basis and the review documented.
5. Access Restriction: Within the security policy of the individual institution, the system should limit access to legitimate users.
6. Archiving: The system shall have adequate back up and archive mechanisms in place.

... (from Yugoslavia)
Glas osiguranika 2000;(21):1-2.
The newly elected Serbian Minister of Health, Dr Nada Kostic, has been working at the Clinical Hospital Center "Dr Dragisa Misovic" since 1984. She specialized in endocrinology. She says that she sees her life, first of all filled with her work with patients but also with giving lectures to students of the Faculty of Medicine. She is supposed to change her title of a docent into the title of a professor, soon, according to the regulations of law.