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Red cell size heterogeneity during ontogeny.

To determine the manner in which erythrocyte changes occur during ontogeny, several red cell parameters were analyzed in fetuses, newborn infants, children, and adults. Although mean cell volume (MCV) and hemoglobin F (HbF) levels decreased as expected during in utero development, the coefficient of variation of red cell size (%CV), or red cell distribution width (RDW), increased from fetuses to newborn infants. In normal adults, the %CV was 15 (RDW was 13). The %CV in fetuses at 18-24 weeks gestation was 18, and it was 21 at term birth. High values for %CV or RDW indicate significant anisocytosis. Erythropoiesis at the time of birth is not a steady-state condition. Erythrocytes of a wide variety of sizes are present, with the appearance of new small cells on a background of older, larger red cells. This increased anisocytosis suggests that these new erythrocytes do not appear to be due to a smooth, continuous evolution of red cell size, but rather to discrete, perhaps clonal, changes.

Adolescent

Adhesive and migratory behaviors of nevus cells differ from those of epidermal melanocytes and are not linked to the histological type of nevus.

It has been postulated that acquired nevi undergo life span continuous evolution from junctional, presumably in radial expanding phase at the dermal epidermal junction, to compound and then to dermal nested nevi. In an attempt to correlate the morphology of nevi with biological data, we have investigated whether migratory and adhesive phenotypes of nevus cells could account for histological patterns and possible spatiotemporal changes in nevi. Nevus cells were cultured from compound and dermal nevi and compared to normal epidermal cultured melanocytes from children and adults. AR nevus cells showed similar in vitro adhesive and migratory indexes on laminin-1, laminin-5/nicein, fibronectin, or collagen IV substrates, suggesting that these intrinsic characteristics do not account for the tendency to dermal nesting and/or to radial growth along the dermal-epidermal junction. The cells from epidermal and dermal parts of compound nevi migrated similarly across a reconstituted basement membrane. The results show that intrinsic adhesive and migratory behaviors of nevus cells were not associated with a histological type of nevus. Interestingly, differences in migratory phenotype and intercellular adhesion capacities between nevus cells and normal melanocytes indicated that they could represent different melanocytic cell subpopulations. Finally, melanocytes from adults and children expressed similar levels of the same integrins as all nevus cells but showed differences in function of both alpha3 and alpha6 integrin subunits and in migratory/adhesive behaviors, which may suggest different states of melanocyte maturation.

Adult

The therapeutic community: exploring the boundaries.

The past 20 years have demonstrated the effectiveness of therapeutic community (TC) treatment for drug abuse as it evolved in the United States. We now better understand the influence that psychodynamic features of TC treatment have on character disorder. Best perceived as a setting designed--as society is not--to encourage and support social learning, the TC has succeeded in modifying its programs and adapting self-help methods to serve drug abusers of all kinds and abusers of all drugs. Continued evolution of the TC depends upon development of its already-demonstrated capacity to affect disordered behaviour other than drug abuse. The growth of disordered populations in the United States and increasingly in Great Britain gives urgency to such future employment. Therapeutic communities and TC-like programs for non-drug abusers already exist. But widespread use depends upon strengthening the theoretical underpinnings of TC treatment and establishing closer working relationships between TC's and mainstream medical, mental health and social service institutions.

Humans

Delayed success following radiofrequency catheter ablation.

Two patients who underwent attempted radiofrequency catheter ablation of an atrioventricular accessory pathway experienced delayed abolition of pathway conduction. During the procedures there was transient block in the accessory pathway following multiple ablation attempts at closely spaced sites. Both patients showed evidence of preexcitation at the conclusion of the ablation session but neither showed evidence of accessory pathway conduction during a second electrophysiological study. These observations demonstrate that in patients in whom transient block of the accessory pathway is produced, continued evolution of radiofrequency energy lesions may result in the eventual success of an initially unsuccessful ablation session.

Adenosine

Behavioral marriage therapy. III. The contents of Gurman et al. may be hazardous to our health.

This paper was written as a reply to a critique of behavioral marital therapy (BMT) by Gurman, Kniskern, and Knudson (6, 7). The reply is divided into four sections. First, the paper addresses the critics' comments on the conceptual model put forth by BMT, correcting and clarifying various misconceptions, and restating some of the basic ideological principles in the behavioral model. Second, the paper discusses behavioral change techniques and technology, along with extratechnological treatment considerations. Again, misrepresentations of BMT are corrected. Third, an analysis of the literature investigating the therapeutic efficacy of BMT is reviewed, and the conclusion is reached that BMT is demonstrably effective, at least for a substantial number of mildly to moderately distressed couples. Criticisms are made of the analysis of the same literature conducted by Gurman et al. We conclude that, contrary to the spirit of the paper by Gurman et al., BMT is a viable framework for conceptualizing and treating relationship problems and that the commitment of its adherents to experimental investigation promises continued evolution, refinement, and improvement.

Behavior Therapy

DNA content in primary tumours and lymph node metastases in colorectal adenocarcinoma.

In 18 consecutive patients operated on for colorectal carcinoma of Dukes' stage C, the DNA patterns were determined in multiple samples of the primary tumours and in all detected lymph node metastases. Single-cell microspectrophotometry on Feulgen-stained smears of fine-needle aspirates was used. When the most aggressive DNA pattern was considered representative, 12 primary tumours (67%) were designated as aneuploid. The frequency of aneuploidy among the metastases was almost the same (63%). In 15 cases (83%) the DNA patterns displayed by the metastatic lymph nodes were also found in the corresponding primary tumour, while in the remaining three cases (17%) the DNA pattern in the lymph node metastases was not seen in any of the multiple samples from the primary tumour. The observed tumour DNA heterogeneity may reflect either the multicellular origin of the tumour cells or the continuous evolution and progression of a neoplasm of unicellular origin, and may partly explain the dissimilarities between the DNA patterns of the primary tumour and the lymph node metastases. Biopsy samples from a number of metastatic lymph nodes are therefore required to ensure representativeness and to permit an adequate analysis of the prognostic role of the DNA ploidy status in lymph node metastases from colorectal cancer.

Adenocarcinoma

Flow cytometric reticulocyte analysis and the reticulocyte maturity index.

Reticulocyte analysis has evolved to one of the accepted and routinely practiced clinical applications of flow cytometry technology. Similar to CD4 measurements, FCM technology has contributed to documented improvements in reticulocyte counting precision over previous microscope-based techniques. The ability to FCM instruments to quantitate fluorescence intensity has been utilized to derive a parameter of reticulocyte maturity, which we have termed the reticulocyte maturity index. The FCM-derived RMI parameter offers an additional perspective to assess the erythropoietic response in anemic patients over reticulocyte counting alone and provides further insight into the differential diagnosis of anemia. Clinical utility of the RMI has been reported in monitoring expensive, new-technology therapies, such as bone marrow transplantation and erythropoietin therapy. FCM reticulocyte analysis is still not fully mature, but is in a state of continued evolution. Needs exist for (i) improved software for data analysis, (ii) newer automation techniques to improve interlaboratory correlations, and (iii) further validation and refinement of the reticulocyte maturity index parameter.

Anemia

Coxsackievirus A6 on the rise: epidemiology, pathogenicity, evolutionary dynamics, and antiviral strategy.

SUMMARYIn recent years, coxsackievirus A6 (CVA6) has become a predominant cause of hand, foot, and mouth disease (HFMD) worldwide, surpassing enterovirus A71 (EV-A71) and CVA16. The rise of CVA6 is of particular public health concern due to its association with atypical and severe clinical presentations, including extensive vesiculobullous eruptions and neurological complications. These diverse and often non-classical manifestations, which also occur in adults, complicate clinical diagnosis and highlight the need for enhanced molecular surveillance. Furthermore, the potential impact of enteroviral infection during pregnancy and on neonatal outcomes remains an important clinical consideration. While both structural and non-structural proteins of CVA6 are known to contribute to viral virulence, the underlying pathogenic mechanisms are not fully understood. Continuous evolution of CVA6 through genetic variation and frequent recombination has led to the emergence of distinct lineages and recombinants, posing substantial challenges to the development of effective antivirals and vaccines. To address these gaps, this review systematically examines the global epidemiology, pathogenic mechanisms, evolutionary dynamics, current diagnostic tools, and antiviral strategies for CVA6. By integrating these perspectives, this work aims to inform public health preparedness and guide future research toward mitigating outbreaks driven by emerging recombinants and novel enterovirus serotypes.

Humans

New classification of peripheral retinal vascular changes in sickle cell disease.

The systemic complications of homozygous sickle cell disease (SS) are more severe than in sickle cell haemoglobin C (SC) disease, and yet visual loss due to proliferative retinopathy is more common in the latter. This anomaly is unexplained. It is believed that proliferative disease occurs in response to closure of the peripheral retinal vasculature, yet a systematic longitudinal survey of the peripheral retinal vascular bed has not been undertaken. In the Jamaica Sickle Cohort study all subjects are scheduled to receive annual ocular examination and fluorescein angiography. The results have now been analysed in subjects with SS and SC disease using a new classification system based on a comparison of the peripheral retinal vascular bed with that recorded in the cohort with normal haemoglobin (AA) genotype. The vascular patterns could be classified as qualitatively normal (type I) or abnormal (type II). An abnormal vascular pattern was identified more commonly with age, in a significantly larger proportion of subjects with SC than SS disease, and was associated with the development of proliferative disease. In order to establish the dynamics of change, the angiograms were analysed in the 18 subjects (24 eyes) who developed proliferative disease. It is shown that a qualitatively normal vascular pattern may be retained despite loss of capillary bed and posterior displacement of the vascular border. A border which is qualitatively abnormal does not revert to normal, and once abnormal, continuous evolution may occur before development of proliferative lesions. The peripheral border of the retinal vasculature was too peripheral to photographed in 13 of the 24 eyes before it becoming qualitatively abnormal. It is concluded that a normal border, if posterior, results from gradual modification of the capillary bed and indicates low risk of proliferative disease. A qualitatively abnormal vascular border occurs as a radical alteration of retinal perfusion in subjects in whom little modification of the vascular bed occurred before the event, and signals risk of proliferative disease. This classification system is useful in identifying the likelihood of threat to vision in young Jamaicans with sickle cell disease, and the higher frequency of proliferative retinopathy in SC can be explained by the higher prevalence of a qualitatively abnormal peripheral retinal vasculature.

Adolescent

Updating the Read Codes: user-interactive maintenance of a dynamic clinical vocabulary.

The Read Codes are a hierarchically-arranged controlled clinical vocabulary introduced in the early 1980s and now consisting of three maintained versions of differing complexity. The code sets are dynamic, and are updated quarterly in response to requests from users including clinicians in both primary and secondary care, software suppliers, and advice from a network of specialist healthcare professionals. The codes' continual evolution of content, both across and within versions, highlights tensions between different users and uses of coded clinical data. Internal processes, external interactions and new structural features implemented by the NHS Centre for Coding and Classification (NHSCCC) for user interactive maintenance of the Read Codes are described, and over 2000 items of user feedback episodes received over a 15-month period are analysed.

Computer Systems

A continuous spectrum of hypercoagulability exists in acute nonlymphoblastic leukemia.

A consumption coagulopathy syndrome has frequently been reported in association with some cases of acute nonlymphoblastic leukemia (ANLL) and mainly in acute promyelocytic leukemia (M3). Eighteen cases of ANLL have been studied on admission, before chemotherapy was started. Levels of antithrombin III (AT-III), protein C (PC), protein S (PS), thrombin-antithrombin complex (T-AT-III), tissue plasminogen activator, plasminogen (Pg), alpha-2-antiplasmin (alpha-2-AP), D-dimer (DD) and fibrinogen (Fg) were determined. The results showed normal levels of AT-III and PS, decreased levels of PC, alpha-2-AP, Pg and Fg in some cases, and an elevation of DD and T-AT III complex in almost all patients. There was a continuous evolution of data from M1 cases in which only slight alterations were seen up to M3 cases where all those pathologic data were observed.

Adult

Psychoanalytic contributions to psychiatric nosology: forms of masochistic behavior.

This paper summarizes the major strengths and weaknesses of current psychiatric nosology, and then discusses various forms of masochistic behavior as one illustration of how psychoanalysis can contribute to the continuing evolution of psychiatric nosology. Masochistic behavior is separated into behavior in which there is a predominantly conscious link between pleasure and pain, and behavior in which that link is predominantly unconscious. Both categories are further separated into normal and pathological forms. The current diagnostic category of dysthymic disorder is then discussed, with consideration given to the contribution that psychoanalysis can make toward the clarification and delineation of this heterogeneous diagnostic category.

Depressive Disorder

Quality management in mental health. II. Managing risk of dangerousness.

In 1995 R. L. Coleman and D. E. K. Hunter described a quality management approach that produced measurable improvements in quality of care in a state-operated psychiatric hospital. Continued evolution of this approach has subsequently enabled the development and implementation of effective processes for managing risk of dangerousness among patients throughout the hospital. Supported by management principles that promote hospital-wide quality improvement, clinicians and managers produced an environment that was conducive to promoting quality. The hospital-wide quality improvement context involved integrating multiple activities designed to promote quality of care, including significant collaborations with other health care organizations. The hospital's mission as an acute care psychiatric facility has required that it focus on assessing and managing risk of dangerousness in a systematic manner. This was done through developing and utilizing a predictive risk assessment instrument and indicators for managerial oversight. This was accomplished in these steps. First, clinical leaders rated potential criteria according to estimates of their ability to predict dangerousness behavior and reviewed their estimates in relation to clinical findings. Second (and concurrently), clinicians and managers implemented procedures to monitor clinical risk and performance. Finally, outcome data were reviewed. They suggested that this approach was effective in reducing risk of dangerous behavior among patients on all psychiatric wards.

Dangerous Behavior

Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques.

The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather than the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines. One of these S2-directed mAbs, CC40.8, has demonstrated protective efficacy in small animal models against SARS-CoV-2 challenge. As the next step in the pre-clinical testing of S2-directed antibodies as a strategy to protect from SARS-CoV-2 infection, we evaluated the in vivo efficacy of CC40.8 in a clinically relevant non-human primate model by conducting passive antibody transfer to rhesus macaques (RM) followed by SARS-CoV-2 challenge. CC40.8 mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n = 6) of RM, alongside one group that received a control antibody (PGT121). Viral loads in the lower airway were significantly reduced in animals receiving higher doses of CC40.8. We observed a significant reduction in inflammatory cytokines and macrophages within the lower airway of animals infused with 10mg/kg and 1mg/kg doses of CC40.8. Viral genome sequencing demonstrated a lack of escape mutations in the CC40.8 epitope. Collectively, these data demonstrate the protective efficiency of broadly neutralizing S2-targeting antibodies against SARS-CoV-2 infection within the lower airway while providing critical preclinical work necessary for the development of pan-β-CoV vaccines.

Animals

The Internet as an information source for geriatricians.

Electronic storage of and access to medical data is becoming increasingly common. Advances in computer technology and telecommunications have made it possible to store vast amounts of information in databases and transmit this information rapidly to any place on the globe. At the forefront of this technology is the Internet, a worldwide computer network that links together over 10 million computers in more than 80 countries. The Internet is an unprecedented information resource. There are tens of thousands of computers on the Internet that are freely accessible to the general public. Commercial organisations, academic institutions and government agencies are just some of the entities that can be accessed through the Internet. There are a large number of medical resources at these sites including electronic journals, online databases and search services, teaching materials, and methods for obtaining online continuing medical education credits. The Internet offers a variety of services such as electronic mail, discussion groups and the ability to log on to and run programs on remote computers. The one service, however, that has been responsible for the phenomenal growth of the Internet is the World Wide Web, the primary focus of this article. The World Wide Web allows a user to view documents that contain text, graphics, images, and movie and sound clips. In addition, any of these elements can be linked to other documents or services anywhere on the Internet. This article gives a general overview of the Internet and the medical resources it contains, with an emphasis on material related to geriatrics and aging. The Internet is in a state of continual evolution, and it is likely that dramatic new capabilities will become available in the near future.

Aged

Recent achievements in the development of radiolabeled monoclonal antibodies for diagnosis, therapy and biologic characterization of human tumors.

Human tumors express antigenic sites that can serve as targets for radiolabeled monoclonal antibodies for diagnosis, therapy and biologic characterization of human tumors in vivo. Over the last decade, nearly 200 clinical trials have been performed which demonstrate that tumors can be detected with excellent sensitivity and specificity. Tumors which are otherwise occult, particularly for colorectal (anti-CEA and anti-TAG-72 antibodies) and ovarian cancer (anti-TAG-72 and anti-HMFG), are detected in a significant fraction of problem patients. Therapy using radiolabeled antibodies has been effective in lymphomas, leukemias and neuroblastomas, and is beginning to show promise in other solid tumors. Biologic characterization of tumors is likely to become more and more important in the future as monoclonal antibodies against oncogene products, such as her-2-neu, are developed. Development of new antibody forms through genetic engineering techniques, and the continual evolution toward higher resolution imaging instruments, such as PET and SPECT, will lead to further clinical improvements in cancer detection.

Antibodies, Monoclonal

The computer-based medical record: current status.

At the turn of the century, neither hospitals nor physicians routinely kept clinical records. Since then, the medical record has gradually evolved. More recently, as society and medicine have become more complex and sophisticated, inadequacies of the paper medical record have become increasingly apparent. The computer-based medical record addresses many of the deficiencies of the paper record. Meanwhile, barriers to computer-based records have decreased; hardware has become more affordable, powerful, and compact, and software has been refined. Socially, the major payers for health care are demanding verification of the effectiveness and quality of care, information that involves data-intensive research. The electronic medical record promises to improve quality of care by providing point-of-care reminder and decision support tools as well as a database for substantiating the effectiveness of care. In conjunction with the growing integration of computers into all facets of life, government agencies, computer giants, and medical organizations are currently laying the groundwork for the development of standardized elements and formats for computer-based medical information systems. As part of the continuing evolution of the medical record, we foresee these forces culminating in the computerization of the clinical record. In this review, we briefly describe the developments that led us to this conclusion and describe computer-based clinical record systems in use in two family practice settings.

Decision Support Techniques

The Science of Unitary Human Beings: a contemporary literature review.

This literature review identifies the origins of the Science of Unitary Beings, explores definitions of the main components of the conceptual framework and highlights the latest developments in its continual evolution. Examples of how nurse researchers and practitioners have interpreted these components and latest developments are given. The author shows that rather than being an obscure and esoteric framework, the Science of Unitary Human Beings has already had a considerable influence on nursing practice, education and research in North America. A prediction is made that in years to come the framework may begin to have the same impact in the United Kingdom.

Humans