Nineteenth- and twentieth-century brain maps relating to locations and constructions of brain functions.

This article is an outline of the transition in "brain maps" used to illustrate locations of cortical "centers" associated with movements, sensations, and language beginning with images from Gall and Spurzheim in the nineteenth century through those of functional magnetic resonance imaging in the twenty-first century. During the intervening years, new approaches required new brain maps to illustrate them, and brain maps helped to objectify and naturalize mental processes. One approach, electrical stimulation of the cerebral cortex-exemplified by Fritsch and Hitzig in 1870, Ferrier in 1873, and Penfield by 1937-required brain maps showing functional centers with expanded and overlapping boundaries. In another approach, brain maps that linked cortical centers to account for the complex syndromes of aphasia, apraxia, alexia, and agraphia were initially constructed by Baginsky in 1871, Wernicke in 1874, and Lichtheim in 1885, then later by Lissauer in 1890, Dejerine in 1892, and Liepmann in 1920, and eventually by Geschwind in 1965 and others through the late twentieth century. Over that intervening time, brain maps changed from illustrations of points on the cerebral cortex where movements and sensations were elicited to illustrations of areas (centers) associated with recognizable functions to illustrations of connections between those areas that account for complex symptoms occurring in clinical patients. By the end of this period, advancements in physics, mathematics, and cognitive science resulted in inventions that allowed brain maps of cortical locations derived from cognitive manipulations rather than from the usual electrical or ablative manipulations. "Mental" dependent variables became "cognitive" independent variables.

The challenges and opportunities for implementing group antenatal care ('Pregnancy Circles') as part of standard NHS maternity care: A co-designed qualitative study.

OBJECTIVE: To identify the challenges and opportunities for rolling out a bespoke model of group antenatal care called Pregnancy Circles (PC) within the National Health Service: what kind of support and training is needed and what adaptations are appropriate, including during a pandemic when face-to-face interaction is limited. DESIGN: Exploratory qualitative study (online focus group). Study co-designed with midwives. Data analysed thematically using an ecological model to synthesise. SETTING: Five maternity services within the National Health Service. PARTICIPANTS: Seven midwives who facilitated PCs. Three senior midwives with implementation experience participated in the co-design process. FINDINGS: Three themes operating across the ecological model were identified: 'Implementing innovation', 'Philosophy of care' and 'Resource management'. Tensions were identified between group care's focus on relationships and professional autonomy, and concepts of efficiency within the NHS's market model of care. Midwives found protected time, training and ongoing support essential for developing the skills and confidence needed to deliver this innovative model of care. Integrating Pregnancy Circles with continuity of carer models was seen as the most promising opportunity for long-term implementation. Midwives perceived continuity and peer support as the most effective elements of the model and there was some evidence that the model may be robust enough to withstand adaptation to online delivery. KEY CONCLUSIONS: Midwives facilitating group care enjoyed the relationships, autonomy and professional development the model offered. Harnessing this personal (micro-level) satisfaction is key to wider implementation. Group care is well aligned with current maternity policy but the challenges midwives face (temporal, practical and cultural) must be anticipated and addressed at macro and meso level for wider implementation to be sustainable. The PC model may be flexible enough to adapt to online delivery and extend continuity of care but further research is needed in these areas. IMPLICATIONS FOR PRACTICE: Implementation of group care in the NHS requires senior leadership and expertise in change management, protected time for training and delivery of the model, and funding for equipment. Training and ongoing support, are vital for sustainability and quality control. There is potential for online delivery and integrating group care with continuity models.

The early history of the knee-jerk reflex in neurology.

Medical interest in the knee-jerk reflex began in about 1875 with simultaneous and independent publications by Wilhelm Heinrich Erb (1840-1921) and Carl Friedrich Otto Westphal (1833-1890) contending that the knee jerk was absent (and the ankle clonus was present) in all clear cases of locomotor ataxia (tabes dorsalis). Physicians in the medical communities of Europe, Great Britain, and North America responded with case and large group studies that tested this contention. These studies revealed the usefulness of the knee jerk and other myotatic reflexes, but also unexpected characteristics. The knee jerk, apparently so simple, proved to be a complex phenomenon depending the strength of the strike on the patella, induced muscle tension, and inhibition from the brain. Was it a reflex with afferent and efferent nerves and an intervening process in the spinal cord, or was it a local phenomenon confined to the muscle itself? Experimental studies directed at the reflex issue investigated latencies from patella strike to leg extension or muscle contraction and compared them with latencies from direct muscle strikes and theoretical calculations based on reflex components. Such studies were unable to resolve the reflex issue during the nineteenth century. The physicians were shown to be limited, like all scientific explorers of the unknown, by their knowledge, methodology, and technology.

Angioleiomyoma masquerading as shoulder pain.

Angioleiomyoma is a benign soft tissue tumor originating from vascular smooth muscle. We report a case of a 20-year-old student who presented with pain in the right shoulder of 4 years duration. Shoulder movements were pain-free throughout the range of motion except resisted external rotation. Magnetic resonance imaging visualized a well-circumscribed lesion over the infraspinatus tendon. The lesion was surgically removed and sent for histopathological analysis. Morphology and immunohistochemistry results were suggestive of angioleiomyoma. The most common location for such a lesion is the lower limb, with less than 1% being reported in the upper arm, of which an angioleiomyoma of the shoulder is extremely rare.

Subclinical cardiovascular disease in HIV controller and long-term nonprogressor populations.

OBJECTIVES: Elite controllers (ECs), viraemic controllers (VCs), and long-term nonprogressors (LTNPs) control HIV viral replication or maintain CD4 T-cell counts without antiretroviral therapy, but may have increased cardiovascular disease (CVD) risk compared to HIV-uninfected persons. We evaluated subclinical carotid and coronary atherosclerosis and inflammatory biomarker levels among HIV controllers, LTNPs and noncontrollers and HIV-uninfected individuals in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS). METHODS: We measured carotid plaque presence and common carotid artery intima-media thickness (IMT) in 1729 women and 1308 men, and the presence of coronary artery calcium and plaque in a subgroup of men. Associations between HIV control category and carotid and coronary plaque prevalences were assessed by multivariable regression analyses adjusting for demographics and CVD risk factors. Serum inflammatory biomarker concentrations [soluble CD163 (sCD163), soluble CD14 (sCD14), galectin-3 (Gal-3), galectin-3 binding protein (Gal-3BP) and interleukin (IL)-6] were measured and associations with HIV control category assessed. RESULTS: We included 135 HIV controllers (30 ECs) and 135 LTNPs in the study. Carotid plaque prevalence and carotid IMT were similar in HIV controllers, LTNPs and HIV-uninfected individuals. HIV controllers and LTNPs had lower prevalences of carotid plaque compared to viraemic HIV-infected individuals. The prevalence of coronary atherosclerosis was similar in HIV controllers/LTNPs compared to HIV-uninfected and viraemic HIV-infected men. Controllers and LTNPs had higher concentrations of sCD163 and sCD14 compared to HIV-uninfected persons. CONCLUSIONS: Subclinical CVD was similar in HIV controllers, LTNPs and HIV-uninfected individuals despite elevated levels of some inflammatory biomarkers. Future studies of HIV controllers and LTNPs are needed to characterize the risk of CVD among HIV-infected persons.

Diving responses elicited by nasopharyngeal irrigation mimic seizure-associated central apneic episodes in a rat model.

The spread of epileptic seizure activity to brainstem respiratory and autonomic regions can elicit episodes of obstructive apnea and of central apnea with significant oxygen desaturation and bradycardia. Previously, we argued that central apneic events were not consequences of respiratory or autonomic activity failure, but rather an active brainstem behavior equivalent to the diving response resulting from seizure spread. To test the similarities of spontaneous seizure-associated central apneic episodes to evoked diving responses, we used nasopharyngeal irrigation with either cold water or mist for 10 or 60 s to elicit the diving response in urethane-anesthetized animals with or without kainic acid-induced seizure activity. Diving responses included larger cardiovascular changes during mist stimuli than during water stimuli. Apneic responses lasted longer than 10 s in response to 10 s stimuli or about 40 s in response to 60 s stimuli, and outlasted bradycardia. Repeated 10 s mist applications led to an uncoupling of the apneic episodes (which always occurred) from the bradycardia (which became less pronounced with repetition). These uncoupled events matched the features of observed spontaneous seizure-associated central apneic episodes. The duration of spontaneous central apneic episodes correlated with their frequency, i.e. longer events occurred when there were more events. Based on our ability to replicate the properties of seizure-associated central apneic events with evoked diving responses during seizure activity, we conclude that seizure-associated central apnea and the diving response share a common neural basis and may reflect an attempt by brainstem networks to protect core physiology during seizure activity.

Henry Herbert Donaldson's (1857-1938) contribution to an organized approach to the experimental study of the mammalian central nervous system.

This article shows that the academic and research careers of Henry Herbert Donaldson (1857-1938) were directed to provide basic information about the growth of the vertebrate nervous system and to provide standards and the means to make such research efficient. He earned the reputation of making the albino rat a standard laboratory animal. His academic career began when he was an undergraduate at Yale University in 1875 and concluded with his death as Professor and Head of the Department of Neurology at the Wistar Institute of Anatomy and Biology of the University of Pennsylvania in 1938. During that period, pivotal experiences occurred, including research in physiological chemistry with Chittenden at the Sheffield School at Yale, graduate study at Johns Hopkins University, postgraduate study in Europe, and professorial positions at Clark University and the University of Chicago. It was at Johns Hopkins University that Donaldson learned about the need for physiological, anatomical, and psychophysical research and about the techniques to allow such research. It was at Clark University that he had first-hand and detailed experience with the anatomy of the brain of a deaf-blind-mute woman, as he attempted to correlate her sensory deficits with her brain development. It was at Clark University that he clearly recognized the need for standardization in neurological research. At the University of Chicago, he developed administrative skills and began a coordinated research effort to delimit the growth of the nervous system. It was at Chicago that he learned that the albino rat could be a reasonable subject for such research. It was also at Chicago that he was able to formulate ideas about the future organizational needs of human neuroanatomy. It was at the Wistar Institute that his research program and his professional career matured. He organized a research effort to elucidate the growth of the nervous system. He contributed to the coordination of neurological research in the United States and Europe. It was while at the Wistar Institute that he became well-known for making the albino rat a standard laboratory mammal-a convenient living material for research.

Procedures and complications in late-nineteenth-century experimental neuroanatomical research exemplified by articles of Henry Herbert Donaldson (1857-1938).

Henry Herbert Donaldson (1857-1938) was a leader in neurological research in the United States for several decades, beginning about 1890. A detailed account of three of his earliest publications shows the neuroanatomical procedures involved in the study of the relation of brain and intelligence during the late-nineteenth-century in America. Two of the articles, published in September 1890 and December 1891, were titled, "Anatomical Observations on the Brain and Several Sense-Organs of the Blind Deaf-Mute, Laura Dewy Bridgman (1829-1889)"; the third, published in August 1892, used the information from the first two to delimit the extent of the visual processing area of the human cortex. Donaldson's procedures included brain cuttings and measures of macroscopic brain structures, histology of cellular structures, attempts to relate macroscopic brain structures with brain functions, data corrections, estimations, comparisons, and statistics. These procedures provide a view of the relative thoroughness, accuracy, and comparability of the various neuroanatomical techniques in use at that time and of Donaldson's implementation of the techniques. Donaldson's brain cutting techniques were much more comparable than his measurement techniques. The latter could be quite precise, but they were fraught with lack of standardized procedures that made corrections and estimations necessary when making data comparisons across studies. Donaldson emphasized these incompatibilities, implying a need for standardization. Statistical procedures were the least thorough and effective. His, and the field's, total complement of statistical techniques consisted of mean and range, which severely limited his ability to make complicated assessments. This limitation was not necessarily supplemented by stringent control group comparisons.

American neurophysiology and two nineteenth-century American Physiological Societies.

This article contrasts two American Physiological Societies, one founded near the beginning of the nineteenth century in 1837 and the other founded near its end in 1887. The contrast allows a perspective on how much budding neuroscience had developed during the nineteenth century in America. The contrast also emphasizes the complicated structure needed in both medicine and physiology to allow neurophysiology to flourish. The objectives of the American Physiological Society of 1887 were (and are) to promote physiological research and to codify physiology as a discipline. These would be accomplished by making physiology much more inclusive than traditionally accepted by raising research standards, by giving prestige to its members, by providing members a source of professional interchange, by protecting its members from antivivisectionists, and by promoting physiology as fundamental to medicine. The quantity of neuroscientific experiments by its members was striking. The main organizers of the society were Silas Weir Mitchell, John Call Dalton, Henry Pickering Bowditch, and Henry Newell Martin. The objective of the American Physiological Society of 1837 was to disperse knowledge of the "laws of life" and to promote human health and longevity. The primary organizers were William Andrus Alcott and Sylvester Graham with the encouragement of John Benson. Its technique was to use physiological information, not create it as was the case in 1887. Its object was to disseminate the word that healthy eating will improve the quality of life.

Laryngospasm, central and obstructive apnea during seizures: Defining pathophysiology for sudden death in a rat model.

Seizure spread into the autonomic nervous system can result in life-threatening cardiovascular and respiratory dysfunction. Here we report on a less-studied consequence of such autonomic derangements-the possibility of laryngospasm and upper-airway occlusion. We used parenteral kainic acid to induce recurring seizures in urethane-anesthetized Sprague Dawley rats. EEG recordings and combinations of cardiopulmonary monitoring, including video laryngoscopy, were performed during multi-unit recordings of recurrent laryngeal nerve (RLN) activity or head-out plethysmography with or without endotracheal intubation. Controlled occlusions of a tracheal tube were used to study the kinetics of cardiac and respiratory changes after sudden obstruction. Seizure activity caused significant firing increases in the RLN that were associated with abnormal, high-frequency movements of the vocal folds. Partial airway obstruction from laryngospasm was evident in plethysmograms and was prevented by intubation. Complete glottic closure (confirmed by laryngoscopy) occurred in a subset of non-intubated animals in association with the largest increases in RLN activity, and cessation of airflow was followed in all obstructed animals within tens of seconds by ST-segment elevation, bradycardia, and death. Periods of central apnea occurred in both intubated and non-intubated rats during seizures for periods up to 33s and were associated with modestly increased RLN activity, minimal cardiac derangements, and an open airway on laryngoscopy. In controlled complete airway occlusions, respiratory effort to inspire progressively increased, then ceased, usually in less than 1min. Respiratory arrest was associated with left ventricular dilatation and eventual asystole, an elevation of systemic blood pressure, and complete glottic closure. Severe laryngospasm contributed to the seizure- and hypoxemia-induced conditions that resulted in sudden death in our rat model, and we suggest that this mechanism could contribute to sudden death in epilepsy.

A contextual analysis of nervous force in medico-scientific and literary writings in English of the nineteenth and early-twentieth centuries.

This study concerns the context of use of the term "nervous force," as it appears in scientific and literary publications in English over the course of the nineteenth century and the first two decades of the twentieth century. The context of use, loss, or waste of nervous force and the context of nervous force as an expression of an attribute are analyzed in 189 scientific and 105 literary writings. Both contexts appeared in literary writings, where nervous force expresses the attributes of strength, forcefulness, vigor, or energy and use, loss or waste of nervous force explains such nonmorbid conditions as why someone is tired or needs rest. Only the context of use-loss-waste appeared in the medico-scientific literature, but here it explained both nonmorbid conditions (for example, effects of old age) and morbid conditions (like epilepsy). Changes in the number of these references give insights into the medico-scientific and the literary disciplines. Discussions include why nervous force is associated with explanation of disease, the persistence of its use in this capacity, and its influence on a similar use in literary writings.

David Ferrier: brain drawings and brain maps.

This chapter has two emphases, one is about the men who influenced the visual representations that David Ferrier (1843-1928) used to illustrate his work on localization of brain functions during the years 1873-1875, namely, Alexander Ecker, John C. Galton, and Ernest Waterlow, and the other is about the nature of medical representations and of Ferrier's illustrations in particular. Medical illustrations are characterized either as pictures, line drawings, or brain maps. Ferrier's illustrations will be shown to be increasingly sophisticated brain maps that contrast with early nineteenth-century standards of medical illustrations, as exemplified by John Bell (1763-1829).

Mean platelet volume is decreased in HIV-infected women.

OBJECTIVES: HIV infection is associated with higher than expected cardiovascular event rates and lowered platelet counts. These conditions are associated with an elevation of mean platelet volume (MPV). The present study compared MPV in HIV-infected and uninfected women and identified factors influencing MPV values in HIV-infected women. METHODS: A total of 234 HIV-infected and 134 HIV-uninfected participants from the Women's Interagency HIV Study (WIHS) had MPV values obtained. HIV-infected women were older, were more likely to have diabetes and had higher triglyceride levels than HIV-uninfected women. RESULTS: The mean platelet count was lower in HIV-infected vs. uninfected women [249 cells/µL (95% confidence interval (CI) 238, 259 cells/µL) vs. 276 cells/µL (95% CI 265, 287 cells/µL), respectively; P < 0.01]. Adjusted mean MPV values were lower in the HIV-infected than in the uninfected group [8.66 fL (95% CI 8.52, 8.79 fL) vs. 9.05 fL (95% CI 8.87, 9.24 fL), respectively]. In multiple regression analysis, after adjusting for other covariates, MPV was positively associated with platelet count, and negatively with HIV infection (model R² = 0.20; P < 0.01). In multiple regression analysis confined to HIV-infected women, a lower MPV was independently associated with a history of AIDS-defining illness (R² = 0.28; P = 0.03), but not with nadir CD4 count or highly active antiretroviral therapy (HAART) use. CONCLUSIONS: HIV-infected women had lower MPV values than uninfected women, suggesting impaired production rather than increased destruction. Higher than expected cardiovascular event rates cannot be attributed to greater platelet reactivity as measured by MPV.

Madelung disease: a rare case associated with gynaecomastia and scrotal involvement.

Madelung disease is rare, and characterised by accumulation of fatty non-encapsulated tissue in the head, neck, shoulders, and upper extremities. The aetiology is not completely known, but the association with alcohol intake is clear. We present a neglected case that was associated with bilateral asymmetrical gynaecomastia. To the best of our knowledge, this is a pattern of involvement not previously reported. The treatment of choice is lipectomy for severe cases and liposuction for less extensive accumulations of fat.

Brain physiology and the mind in the nineteenth century.

This article explores the integration of research and theory in nineteenth-century neurophysiology. Four generalities combine to explain their integration. They are the core beliefs of the neurologists, the pervasive habit of perceiving mind when observing behavior, the criteria for the existence of mind, and mind as an efficient cause. These generalities help explain specific choices made by certain researchers to work within the traditional model of the nervous system, to reject materialism, and to find intelligence and voluntary behaviors in physiological systems.

First Report of Raspberry bushy dwarf virus Infecting Grapevine in Hungary.

Raspberry bushy dwarf virus (RBDV) is the sole member of genus Idaeovirus and naturally infects Rubus species worldwide. It can be experimentally transmitted to many dicotyledonous plant species from different families. In Slovenia it has been reported to naturally infect grapevine, the first known non-Rubus natural host (3). However, RBDV from red raspberry and grapevine were found to be different in biological, serological, and molecular characteristics (4). From 2007 to 2010, grapevine (Vitis vinifera L.) vineyards were sampled in different parts of Hungary and tested for RBDV infection by double antibody sandwich (DAS)-ELISA using commercial reagents (Bioreba, Reinach, Switzerland). Overall, 181 samples were collected from 10 vineyards around Csörnyeföld, Badacsony, Eger, Tolcsva (Orémus), and Nagyréde. Samples were taken randomly unless plants showing virus-like symptoms were present, which were preferentially included in the survey. Two samples collected in 2010, each consisting of five leaves from five individual plants, tested positive by DAS-ELISA. They originated from a small private vineyard of Italian Riesling, Pinot Gris, and Rhein Riesling in the southwestern part of Hungary near Csörnyeföld where 29 samples were collected. All leaves were asymptomatic. Total RNA was extracted from positive samples using a RNeasy Plant Mini Kit (Qiagen, Hilden, Germany). cDNA was synthesized using primer RNA12 as described (4) and further amplified by PCR using primers RBDVUP1/RBDVLO4 that amplified an 872-bp fragment of RBDV coat protein and 3' non-translated region (2). Amplification products from both samples were directly sequenced (Macrogen, Seoul, Korea). The sequences showed 98.6% identity between each other and were deposited in GenBank (Accession Nos. JQ928628 and JQ928629). Sequences were also compared with RBDV sequences deposited in GenBank. They showed 97.7 to 99.3% identity with RBDV sequences from grapevine from Slovenia and 94.2 to 96.1% with RBDV sequences from Rubus sp. Natural infection of grapevine with RBDV was first reported from Slovenia in 2003 (3) and was recently reported also from Serbia (1). To our knowledge, this is the first report of RBDV infection of grapevine in Hungary and suggests a wider presence of the virus in the region. References: (1) D. Jevremovic and S. Paunovic. Pestic. Phytomed. (Belgrade) 26:55, 2011. (2) H. I. Kokko et al. BioTechniques 20:842, 1996. (3) I. Mavric Plesko et al. Plant Dis. 87:1148, 2003. (4) I. Mavric Plesko et al. Eur. J. Plant Pathol. 123:261, 2009.

Aneurysm-related mortality rates in the US AneuRx clinical trial.

BACKGROUND: The AneuRx (Medtronic) stent graft was approved by the FDA in September 1999. The purpose of this study was to ascertain the aneurysm-related mortality rate of a subgroup of the patient cohort from Medtronic's investigational premarket study. STUDY DESIGN: There were 931 study subjects, from 19 medical centers, who were followed for an average of 3.48 years. Abdominal aortic aneurysm (AAA)-related mortality rates were examined, using death certificates and medical records. RESULTS: The 1-month postimplant death rate was 1.61%. Not counting deaths related to the initial implant, there was an increase in the rate of AAA-related mortality after 3 years, from an average of 0.18% in the first 3 years to an average of 1.39% in years 4 and 5. CONCLUSIONS: Mortality in patients implanted with an AneuRx graft (as determined in this study) probably exceeds that of open procedure patients (based on medical literature) at some point in time, likely within 4 years after implant.