Showing papers in "Yale Journal of Biology and Medicine in 1986"

The Body in Pain: The Making and Unmaking of the World.

Abstract: basic research and clinical data in an attempt to derive a cohesive model which explains the behavioral effects of the drug. Johnson is an experimental psychologist, and his work underlies many of the chapters which suggest that lithium decreases the behavioral response to novel external stimuli. He then utilizes this foundation to propose a cognitive model for lithium's anti-manic action, its inhibition of violent impulsivity, and its prophylactic effects in recurrent depression. Previous formulations which were clinically based, such as that of Mabel Blake Cohen and her associates, stressed the primacy of depression and noted the \"manic defense\" as an attempt to ward off intolerable depression. In direct contrast, Johnson views mania as the primary disturbance in bipolar disorder. He considers depression in bipolar disease as an over-zealous homeostatic inhibitory responsf to a maniaassociated cognitive overload. Consistent with this, he believes, lit lum exerts its anti-manic effect by decreasing cognitive processing in a manner analogous to his animal studies. Johnson also suggests that lithium exerts its prophylactic effect in recurrent depressions by treating subclinical mania. These concepts are supported by the work of Johnson's associate, Kukopulos, to whom the book is dedicated. The bulk of the research which describes the cognitive disturbance in mania is complex, however, and uncomfortably open to multiple interpretations. Recognized as a preliminary effort, Johnson's formulation may help to guide further research. Although Johnson clearly traces lithium actions through a broad range of subjects, his discussion of the neurophysiological aspects of this drug is notably spotty. In particular, Johnson ignores the work of Svensson, DeMontigny, Aghajanian, and others who suggest that serotonergic systems may play an important role in the antidepressant actions of lithium. As a result, he fails to discuss one of the most important current uses of lithium: as an agent used in conjunction with antidepressant medications to increase treatment response in medication-resistant forms of depression. Lithium augmentation of antidepressant medication also challenges the formulation presented by Johnson. This formulation suggests that lithium should have no therapeutic value in patients, such as those with endogenous depression, who already \"under-process\" cognitive information. The omission of lithium augmentation in depression is clearly unfortunate in this text. Overall, this volume demonstrates the benefits of a single-authored text. It it clearly organized and readable. The bibliography is also broad and useful. In this book, Johnson primarily addresses a research audience, and his model seems designed to stimulate thought rather than to improve clinical technique. In this capacity, his book will be of most interest to behavioral psychologists. Other books, focusing purely on clinical data, may be more useful to clinicians. Nevertheless, the clear organization, the large bibliography, and the thoughtful presentation may make this text a useful addition to a clinical library as well.

The adult respiratory distress syndrome.

Abstract: The adult respiratory distress syndrome (ARDS) represents a common denominator of acute lung injury leading to alveolar flooding, decreased lung compliance, and altered gas transport. In the absence of specific etiology and therapy, the management of ARDS remains largely supportive. Ubiquitous use of intermittent positive-pressure ventilation with positive end-expiratory pressure (PEEP) improves arterial oxygenation but with some risk of pulmonary barotrauma and decreased cardiac output. The recent understanding of lung inflation as a modulator of right heart afterload and the effect of the right ventricle on global cardiac performance continues to redefine optimal patterns of ventilatory and hemodynamic intervention in ARDS.

Prostaglandin E as the neural mediator of the febrile response.

Abstract: The evidence favoring a role for prostaglandin E (PGE) as the neural mediator of the febrile response is reviewed and considered under five different essential criteria which would need to be satisfied, if such a role is to be accepted. These criteria are: the ability of intracerebrally microinjected exogenous PGE to cause fever; the detection of increased levels of endogenous PGE in the brain during the normal production of fever; the ability of substances that inhibit the production and release of PGE to block normal fevers; the ability of substances that are specific PGE antagonists to inhibit normal fevers; and the identification of a specific site and cell type for the release of PGE in response to the action of pyrogens. Evidence from the literature that supports these criteria is reviewed and presented in this format, and the conclusion is drawn that the evidence available is more than sufficient to support the initial hypothesis.

Is fever beneficial

Abstract: Fever, the regulation of body temperature at an elevated level, is a common response to infection throughout the vertebrates, as well as in many species of invertebrate animals. It is probable that fever evolved as an adaptive response to infection hundreds of millions of years ago. Many components of the nonspecific and specific host response to infection are enhanced by small elevations in temperature. Perhaps more important, studies of bacterial- and viral-infected animals have shown that, in general, moderate fevers decrease morbidity and increase survival rate.

Effects of human interleukin-1 on natural killer cell activity: is fever a host defense mechanism for tumor killing?

Abstract: Interleukin-1 (IL-1) represents a family of polypeptides with a wide range of biological activities. cDNA from two gene products has been cloned; there are probably more. The human IL-1 family plays an important role in the pathogenesis of many diseases and functions as a key mediator of host response to various infectious, inflammatory, neoplastic, and immunologic challenges. Recombinant mouse (pI 5) and recombinant human (pI 7) IL-1s are being used to confirm the multiple biological properties of IL-1s. Some IL-1 biological activities seem to be involved with mechanisms of host tumor killing. Incubating purified or recombinant human IL-1 with human peripheral blood mononuclear cells in the presence of IL-2 or interferon-alpha results in a synergistic enhancement of certain tumor cells. More recent results indicate that IL-1 exhibits direct cytotoxicity for tumor cells in vitro. The peripheral blood mononuclear cells of patients with tumors demonstrate decreased production of IL-1 when challenged with endotoxin and show a comparable decrease in natural killer activity; adding exogenous IL-1 reverses this defect in these patients. However, induction of hepatic acute-phase proteins such as serum amyloid A serves as a negative feedback since the amyloid protein suppresses natural killer activity. Moreover, natural killer cell activity in the presence of IL-1 or interferon-alpha is suppressed by incubating temperatures of 39 degrees C. This effect is not reversed by inhibitors of prostaglandin synthesis. IL-1 is clearly important to host defense against malignancy, but some aspects of IL-1 biology seem to exert a contrary influence.

Is prostaglandin E2 involved in the pathogenesis of fever? Effects of interleukin-1 on the release of prostaglandins.

Abstract: Interleukin-1 (IL-1) induces the formation of PGE2 from monocytes, fibroblasts, muscle cells, and brain tissue by increasing the intracellular concentrations of CA2+; this cation, in turn, activates a phospholipase which cleaves arachidonic acid from either diacylglycerol or a membrane phospholipid. In addition, IL-1 increases the synthesis of cyclooxygenase, as evidenced by the increased conversion of arachidonic acid into prostaglandins after fibroblasts are pre-incubated with IL-1. Evidence is also presented that fever is caused by interleukin-1-induced prostaglandin E2.

Fever: is it beneficial?

Abstract: Data obtained in lizards infected with live bacteria suggest that fever may be beneficial to their survival. An adaptive value of fever has also been inferred in mammals, but the results are equivocal. Findings that certain leukocyte functions are enhanced in vitro at high temperatures have provided a possible explanation for the alleged benefits of fever. However, serious questions exist as to whether results from experiments in ectotherms and in vitro can properly be extrapolated to in vivo endothermic conditions. Indeed, various studies have yielded results inconsistent with the survival benefits attributed to fever, and fever is not an obligatory feature of all infections under all conditions. Certainly, the widespread use of antipyretics, without apparent adverse effects on the course of disease, argues against fever having great benefit to the host. In sum, although fever is a cardinal manifestation of infection, conclusive evidence that it has survival value in mammals is still lacking.

Is fever beneficial to the host: a clinical perspective.

Abstract: Fever is a phylogenetically ancient host response to infection, being found in fish and lizards, and conserved, with all its metabolic costs, in the higher mammals, including man. The conservation of the fever response in evolution is used as an argument for its survival value and, indeed, in experiments with cold-blooded animals "behavioral fever" has been demonstrated to reduce mortality associated with infection. Recent advances in the biology of interleukin-1 and other cytokines have allowed the testing, in vitro, of components of mammalian host defense (such as immune cell function) at temperatures typical of fever, and marked effects have been found. It remains to be demonstrated, however, that the hyperthermia of fever has survival value in man, and though it might be predicted that fever would be beneficial in infections, it is quite possible that in some circumstances even mild fever could be construed as harmful. In autoimmunity, for example, increased T-cell activation at febrile temperatures may well accelerate disease progress.

Is prostaglandin E the neural mediator of the febrile response? The case against a proven obligatory role.

Abstract: We have reviewed the evidence in favor of a prostaglandin mediator of the thermal responses in fever and found that PGE injected into the hypothalamus does not always cause fever, that cerebrospinal fluid concentrations of PGE are not reliable reflections of hypothalamic events, and that antipyretic drugs may act in ways other than inhibiting PGE synthesis. Fever is not blocked by prostaglandin antagonists, nor by ablation of PGE-sensitive areas of the brain. There is poor correlation between the effects of pyrogens and of PGE on cerebral neurons. There is evidence that at least one prostanoid other than prostaglandin is a mediator of fever, but the prostanoid has not been identified yet. We conclude that PGE may contribute to the neural responses in fever but is not essential.

Prostaglandin E2 and fever: a continuing debate.

Abstract: Prostaglandin (PG) E2 is a potent hyperthermic agent and has been assigned an intermediary function in the response of thermoregulatory neurons to pyrogens. Though attractive, this idea has been challenged on several grounds. The present study confirms that brain PGE2 synthesis increases during fever, the time course of the elevation according with a causative role of the compound. Our experimental data also argue against the involvement of a second cyclooxygenase product, specifically thromboxane (TX) A2, in the action of pyrogens. The sequence of events leading to PGE2 production and fever differs depending on the pyrogen, bacterial vs. leucocytic, and its route of administration. Blood-borne interleukin-1 (IL-1) acts on a discrete site in the central nervous system (CNS) which is tentatively identified with the organum vasculosum laminae terminalis (OVLT). The same site may also be the target for blood-borne endotoxin. In addition, endotoxin may promote PGE2 synthesis in the cerebral microvasculature. Both pyrogens, on the other hand, act diffusely throughout the CNS when given intrathecally. We conclude that PGE2 is well suited for an intermediary role in the genesis of fever and ascribe the reported inconsistencies to methodological factors.

Fever in mammals: is it beneficial?

Abstract: Fever appears to protect ectotherms against infectious disease perhaps because it increases their aerobic metabolic capacity, which is temperature-dependent. Mammals, however, have a high aerobic capacity and normally regulate a high body temperature. Thus, the further increase in temperature induced by interleukin-1 may be dangerous, and the resulting increase in aerobic capacity may not be necessary for an effective defense. In fact, recent evidence suggests that although the neuroendocrine cold defense responses that are stimulated in fever enhance the defenses of the host, the increase in temperature harms these defenses. Data, however, are scarce and equivocal, and the function of fever in mammals is still uncertain.

The Human Skeleton.

Abstract: \"current treatment\" provides 26 references, of which only two were published in 1983, and the others, earlier still. Overall, this is a succinctly written, well-organized treatise of relevance to clinicians interested in the diagnosis, pathophysiology, and treatment of coronary artery spasm. It could inspire an interest in the subject by students at all levels, as well as serving as an adequate reference source. It is difficult, however, to give an unqualified endorsement to a text already out of date at publication.

Multiple primary cancers in Denmark 1943-80; influence of possible underreporting and suggested risk factors.

Abstract: The risk of developing a second primary cancer was studied among 171,749 men and 208,192 women who were reported to the Danish Cancer Registry between 1943 and 1980. Only those who survived at least two months were included in the analysis, and more than 1.7 million person-years of observation were accrued. Altogether, 15,084 second primary cancers developed, of which 13,231 were in organs other than the initial or adjacent site [relative risk (RR) = 1.01]. Adjustment for possible underreporting of multiple primary cancers increased the RR to 1.24, which stresses the need for detailed knowledge of registration procedures interpreting results from cancer registries. The unadjusted RR for all sites increased with time, from 0.94 during the first decade of follow-up (excluding the first year) to 1.13 among 30-year survivors, whereas the adjusted RR increased from 1.08 to 1.41. Elevated risks were observed for sites thought to have a common etiology. For example, cancers of smoking-related sites were increased in both directions following cancers of the oral cavity, respiratory tract, and urinary organs. For cancers suspected to have a hormone- or dietary fat-related association, significant reciprocal relationships were seen among cancers of the endometrium, ovary, and colon. Cancer treatment probably is an important factor in second cancer development, even when judged indirectly in the present study. For example, radiotherapy may have been responsible for an elevated risk of subsequent cancers of the thyroid, breast, colon, rectum, bladder, and connective tissue in long-term survivors. Chemotherapy may have increased the risk of subsequent leukemias. Our data further indicate that cancer patients have no general susceptibility to develop new malignant tumors, although high rates may be found for particular sites sharing common risk factors. Conversely, the occurrence of one cancer does not appear to protect against developing a new cancer.

Multiple primary cancers in Connecticut, 1935-82.

Abstract: Recently, the National Cancer Institute published a comprehensive monograph on multiple primary cancers in Connecticut and Denmark. This paper summarizes some of the observations made on the Connecticut population. Data compiled by the Connecticut Tumor Registry have extended our knowledge about the patterns of multiple primary cancers, especially among long-term survivors of cancer and among patients with relatively rare tumors about which little information currently exists. When compared with the general Connecticut population, cancer patients had a 31 percent (RR = 1.31) increased risk of developing a second cancer and a 23 percent (RR = 1.23) elevated risk of second cancer at a different site from the first. Common environmental exposures seemed responsible for the excess occurrence of many second cancers, particularly those related to cigarette smoking, alcohol consumption, or both. For example, persons with epithelial cancers of the lung, larynx, esophagus, buccal cavity, and pharynx were particularly prone to develop new cancers in the same or contiguous tissue throughout their lifetimes. Cancers of the colon, uterine corpus, breast, and ovary frequently occurred together, suggesting underlying hormonal or dietary influences. Only patients with prostate cancer were at significantly low risk for second cancer development; this might be an artifact of case finding, since advanced age at initial diagnosis was generally associated with an underascertainment of second cancers. Radiotherapy may have caused rectal and other cancer among patients with cancers of the female genital tract, and leukemia among patients with uterine corpus cancer. Chemotherapy with alkylating agents probably contributed to the excess of acute nonlymphocytic leukemia following multiple myeloma or cancers of the breast and ovary. Genetic susceptibility seemed to explain some tumor complexes, such as the multiple occurrences of cutaneous melanoma and the excess of bone cancer following retinoblastoma. Research into multiple cancer syndromes should enhance our understanding of carcinogenic factors and mechanisms and the development of strategies for cancer prevention and control.

The cardiac filling pressure following exercise and thermal stress.

Abstract: Under heat stress, a decrease of the central venous pressure (CVP) was regularly observed, raising the question of whether this reaction is a limiting factor for the circulation. In animal experiments it could be shown, however, that despite a lowered CVP, which depended on the elevated body temperatures, a high cardiac output (CO), as well as an elevated stroke volume could be maintained. A low CVP went hand in hand with a low total peripheral resistance. It was argued that under these circumstances the low CVP was not limiting because the intrinsic factors of the heart (sympathetic stimulation) were capable of maintaining a high CO. In human experiments the lowered CVP had to be seen in relation to the degree of dehydration. Regardless of whether the plasma volume remained constant, as in exercise, or declined, as in thermal stress (sauna), the CVP followed the volume depletion of the vascular and extravascular space, and it might well be that under these circumstances CVP is limiting. In this case, however, the altered CVP must be seen first as a monitor for the fluid deficit and not as a factor controlling cardiac function.

Immune mechanisms and host resistance in the trauma patient.

Abstract: Sepsis is responsible for 75 percent of late deaths following major thermal injury or traumatic injury. Efforts to prevent and/or control sepsis should include an understanding of normal host resistance, proper resuscitation techniques, and nutritional support. Recent studies identifying T suppressor cell abnormalities in burn patients and macrophage defects in trauma patients are presented in this paper. Concluding remarks regarding future directions for research and therapy in this area are also made.

AIDS in the Mind of America. The Social, Political, and Psychological Impact of a New Epidemic.

Abstract: Today's medical journals teem with articles on AIDS, many of them elucidating the gene structure of the HTLV-III virus or describing yet another bizarre complication of the disease. Yet the story of AIDS involves much more than laboratory notebooks and medical charts reveal. AIDS inflicts anguish and social ostracism upon its victims, and the medical establishment has been criticized for being insensitive to these aspects of the disease. Dennis Altman writes about these broader areas of the epidemic in AIDS in the Mind ofAmerica. Altman is a political scientist, and he adequately addresses the social and political issues of the AIDS crisis. He reminds us of the early theories, such as the religious right's insistence that AIDS is the wrath of God thrown upon gays, or a theory attributed to Norman Geschwind, which postulated that gays have a special immune configuration based on sex hormone status during pregnancy which alters both their sexuality and immune system. Altman's section on the public response to AIDS is also thorough. He contrasts the exemplary efforts of the city of San Francisco with the sluggish ones of New York City. He recounts the delays in awarding grants for AIDS research and touches upon the politics of research and the difficulties between the French and American research groups. He gives deserved credit to the gay community, which led the way in providing support services for AIDS patients. The main failing of the book is its style. Altman quotes other writers extensively, and his own text is very dry. In depicting the psychological aspects of the epidemic, it is as if Altman were trying to recite poetry by a mathematical equation. (Larry Kramer's play, The Normal Heart, relates the same message but with much more feeling.) AIDS in the Mind of America tells the broad story of the AIDS crisis, but it does so in the style of laboratory notebooks and medical charts.

The biomedical and epidemiological characteristics of asbestos-related diseases: a review.

Abstract: The purpose of this paper is to provide the reader with an overview of the biomedical and epidemiological characteristics of asbestos-related disease based upon currently available information. Epidemiological and experimental data developed over the past 20 years have greatly added to our knowledge of the biological effects of asbestos, particularly in relation to clinical disease. This information has substantially strengthened the evidence linking asbestos to specific health effects. Lung cancer and mesothelioma are clearly the most important asbestos-related causes of death among exposed individuals, although the accumulated data is suggestive of the existence of an excess risk of gastrointestinal and a variety of other neoplasms. Animal studies confirm the human epidemiological results and indicate that all commercially available fiber types are capable of producing lung cancer and mesothelioma. Experimental implantation and injection studies also show that the carcinogenicity of mineral fibers (including asbestos) is directly related to their dimensionality and not their chemical composition. Although the asbestos-related medical and scientific literature is voluminous, many issues related to the biological activity of asbestos fibers are as yet unresolved. Due to experimental and analytical limitations, questions concerning risk at low-level exposure, dose-response relationships, and individual susceptibility remain problematic.

Pocket Atlas of Human Anatomy.

Abstract: This 184-page text, in the words of the authors,\" has been written to assist medical students, residents, pediatricians, nurses, and family practitioners in developing appropriate hypotheses and a differential diagnosis.\" To this end, it will certainly prove to be very helpful. The volume contains 51 alphabetically listed chapters (six more than the first edition), each dealing with a specific sign or symptom such as anemia, edema, otalgia, or stridor. Every chapter offers a brief overview of the topic, including a recommended \"approach\" to the problem and a thorough differential diagnosis. Most chapters also contain a diagnostic table in which associated signs and symptoms are listed, along with a numbered score (I to 4) that indicates how likely it is to find a certain sign or symptom associated with a specific disease. For example, in the chapter on dysuria one of the table entries is pyelonephritis, which is likely to be associated with flank pain, pyuria (each receiving a 4), fever (receiving a 3), but not with urgency or hesitancy (each receiving a 0). The book is handy, portable, and, though it is not exhaustive, its differential diagnoses are thorough and address a wide variety of pediatric presenting complaints. In short, it goes a long way toward fulfilling the goal proposed by its authors.

Multiple primary malignant neoplasms in England and Wales, 1971-1981.

Abstract: In the period 1971-81, more than 1.9 million persons were registered with a malignant neoplasm among the 49.2 million population of England and Wales. For 63,536 people, two or more tumor registrations (multiple tumor records) have arisen in that period. Because of the structure of the National Cancer Registration scheme, some errors in registration are inevitable, particularly duplicate registration of a single tumor by adjacent regional cancer registries. A pilot study showed that 61 percent of multiple records would represent true multiple primary malignancy, and that these records could be readily separated from registration errors. After abstraction of identifying codes from each tumor, 129,047 tumors involved in 63,536 multiple records were matched to the national cancer file, and the full data set extracted for successfully matched tumors. Person-years data were extracted for the 1.8 million tumors not involved in a multiple record. Eleven percent of multiple records were not completely matched, and a further 16 percent were excluded on SEER criteria, or as probable registration errors, leaving 46,155 multiple primary tumors for further analysis. Over 3 million person-years at risk of a second tumor were accrued. The overall risk of a second tumor at any site before age 85 was 0.77 for males and 0.80 for females, after exclusion of second tumors observed within 12 months of the first. The risk of a new primary apparently decreased with increasing duration of survival, a trend which may be due in part to under-registration of second tumors in the early 1970s and an improvement in linkage since 1971.

Methodologic perspectives on the study of multiple primary cancers

Abstract: Investigations of the patterns of occurrence of multiple primary cancers of the same organ or of different organs provide important data concerning the carcinogenic potential of various therapies used in the treatment of cancer. Associations between cancers arising in different organs may also suggest hypotheses concerning shared risk factors that are strongly related to the incidence of both types of tumors. Studies of multiple primaries of a single organ permit exploration of a number of questions of etiologic interest. First, a strong same-site association over and above what would be expected on the basis of known risk factors suggests that the unexplained proportion of cancer incidence represents relatively stable characteristics of individuals rather than sporadic events. Second, detailed comparisons of risk factors for first versus second primaries of a particular site may help to identify etiologically distinct subtypes of the disease. Third, even if distinct subtypes do not exist, the study of risk factors for a second primary among those who have had a first primary of the same site may enhance the detection of the etiologic role of a particular exposure. Such detection is enhanced when the effects of the exposure are modified by some other factor that is itself a strong risk factor but that is not measured. Finally, studies of multiple primaries of a single site are of particular benefit to clinicians who must decide on appropriate levels of surveillance and preventive intervention.

Emerging roles for cancer registries in cancer control.

Abstract: Cancer registries are a vital part of the national cancer effort to cut United States cancer mortality rates in half by the year 2000. Registries provide the data to focus programs and monitor progress. Success in meeting the year 2000 goal will require aggressive attention to the opportunities for prevention, early detection, treatment, and applied cancer control research, all of which complement the current emphasis on basic research.

Hospital-acquired gangrenous mucormycosis.

Abstract: A post-operative diabetic patient who had been treated for Serratia marcescens bacterial sepsis developed recurrent thrombosis of the left femoral artery following intra-arterial instrumentation. Pathological examination of arterial thrombus ultimately demonstrated invasive mucormycosis of the femoral artery and cultures of this material grew Rhizopus oryzae. The occurrence of cutaneous and subcutaneous mucormycosis is reviewed, as well as recently recognized nosocomial risk factors for mucormycosis, such as elasticized bandages and wound dressings.

Risk of infection following penetrating abdominal trauma: a selective review.

Abstract: Post-operative infectious complications following penetrating abdominal trauma are a major cause of morbidity and contribute significantly to increased length of hospitalization and costs of patient care. Our recent study suggests the individual patient's probability of major infection following traumatic intestinal perforation is high and can be predicted from risk factors identified at the time of surgery. The determinant of primary importance for development of infection confirmed by this study is peritoneal contamination by intestinal contents. Other significant risk factors (p less than 0.05) were number of organs injured, number of units of blood administered, ostomy formation for left colon injury, and the patient's age. Risk of infection can be calculated from these data and could potentially be used to guide post-operative decisions. Areas of trauma care in which alteration of therapy might result in significant savings include choice of antibiotics, duration of antibiotic administration, and wound management. This study supports the use of standardized operative procedures and parenteral antibiotics effective against endogenous aerobic and anaerobic organisms. If such observations continue to be supported by further randomized prospective studies, there is tremendous potential to further tailor surgical management for the individual patient in a more cost-effective manner.

An inquiry into the role of cardiac filling pressure in acclimatization to heat.

Abstract: During the first exposure of exercising subjects to hot environments (30-50 degrees C), cardiac output, heart rate, and body temperature increase over that seen in cool environments, while stroke volume decreases. If daily heat exposures occur, during the second heat exposure, heart rates and rectal temperatures are decreased from day 1 while cardiac output is maintained. This decrease in physiological strain occurs with little or no increase in evaporative heat loss. The alleviating agent appears to be an expansion of plasma volume. Several brief studies have indicated decreases in cardiac filling pressure during exercise in heat, and though inferential, it appears that the progressive increase in plasma volume during the first five to six days of heat exposure assists in maintaining cardiac filling pressure. Later, with increased evaporative heat loss due to increased sweat secretion, the mechanism of supplying increased volume to maintain cardiac filling is changed; fluid is transferred from extravascular to intravascular compartment, thus protecting venous return and cardiac filling pressure. These statements are based on limited data, and there is need of experiments designed to confirm or deny certain conclusions as to the role of cardiac filling pressure in acclimatization to heat.

The first fifty years of the Connecticut Tumor Registry: reminiscences and prospects.

Abstract: The first fifty years of the Connecticut Tumor Registry (1935-1985) have seen unprecedented progress in the collection of standardized data on cancer patients and in the processing of these data, from paper documents to punch cards and magnetic tapes. The need for collecting such information was first recognized, in the early 1930s, by a group of physicians, health professionals, and laymen in New Haven who observed alarming increases in cancer rates and poor survival of cancer patients in this city. This paper recalls the growth and development of the registry and the role played by the Connecticut legislature, the State Medical Society, the Connecticut Department of Health, and the National Cancer Institute in this process. For half a century, the registry has provided assistance to practitioners, hospitals, and research scientists, not only in Connecticut but across the country and around the world. By making available reliable data on incidence and survival, the registry has played a key role in patient management, clinical trials, and etiologic studies. It has also demonstrated the value and served as an exemplary model of a population-based registry. At this juncture in its history, prospects for the future of the Connecticut Tumor Registry appear bright. Its data base will be an essential resource for the recently established Cancer Control Research Unit (CCRU) in the state and for new intervention studies by investigators at Yale, the University of Connecticut, and the State Health Department.

Chemical Neurobiology. An Introduction to Neurochemistry.

Abstract: Over the past few years, research in the area of neurosciences has come more and more to represent the ideal of an integrated approach to the subject. This, in turn, has led to the introduction of undergraduate courses in neurosciences with the consequent appearance of several textbooks with this subject in the title. Naturally, in such taught courses, neurochemistry has taken its place as an important component. However, examination of the texts available reveals that many of them contain little, if any, neurochemistry. Clearly there is a need to fill this gap, and the present book is pitched at just the right level to meet the neurochemical needs of students taking neuroscience courses as third-year undergraduates. The book will doubtlessly also prove most useful as a text for teachers of less advanced students. The first two chapters deal with the structural organization of the brain and include a nice treatment of the biochemical view of the blood-brain barrier. The chapter on brain glucose and energy metabolism is perhaps briefer than one would have liked (the result of selection in a singleauthor text), but nevertheless space is found for descriptions of the use of n.m.r. and positron-emission tomography. The heart of the book, and its particular strength, are the sections on neurotransmission. Here, there are chapters on ‘classical’ neurotransmitters (but in which the author includes the purines), neuropeptides, the preparation and uses of synaptosomes and on synapses. These chapters deal first with the general identification of transmitters, the mapping of pathways containing them (the diagram illustrating the peroxidase-antiperoxidase technique would have been improved if the various antibodies in the ‘sandwich’ had been shown as bivalent) and mechanisms of action (inositol phospholipids are listed in the index and dealt with in the text but the more common name of phosphatidylinositol is not used). Next there is a detailed consideration of individual transmitters, with considerable emphasis placed on the use of pharmacological agents. The chapter on peptides is well-presented, with the emerging importance of vaso-active intestinal peptide and cholecystokinin well represented. In view of the research interests of the author it comes as no surprise that the chapter on synaptosomes is of a high standard with a clear indication of the information one may obtain by use of this preparation. The final two chapters deal with central transmitters and behaviour, and the failure of transmitter systems in brain disorders. When one puts the many good things in the text together with the high standard of figure reproduction to be expected of a Freeman book, it becomes clear that the text can be thoroughly recommended to anyone taking a course in neurosciences or simply entering the field of neurochemistry.

The Psychopharmacology of Lithium.

Abstract: however, somewhat outdated. This volume is organized into four sections. The first section discusses the physiology of binocular vision and oculomotor coordination. That section was originally written by Burian in 1970, and is outdated in places because more recent research has clarified some of the older questions. While the chapters in the portion on binocular vision are excellent, some of the areas pertaining to the physiology and neuroanatomy of eye movements are not current. For instance, in the chapter on physiology of ocular movements, although a number of older techniques and devices are illustrated, the newer and highly popular magnetic search coil technique of measuring eye position is omitted. Similarly, the \"pulse-step\" mechanism for the generation of saccades is not discussed, nor is the superior colliculus mentioned as a site for the coordination of head and eye movements. Although prefaced by a statement to the effect that a detailed knowledge of oculomotor neuroanatomy is not essential for the diagnosis and treatment of strabis-mus, the chapter on neuroanatomy is poor. Its references date between 1897 and 1969. This fact would seem to indicate that the chapter has not been updated since the first edition, although understanding of the complex interactions between visual and oculomotor systems in the brain has been greatly expanded. The old belief that the frontal eye fields are concerned only with horizontal movements is no longer held to be true. The idea that the crossed corticofugal pathway is excitatory while the uncrossed component is inhibitory to the respective ocular muscles is based upon the belief that the frontal eye fields project directly to the abducens nuclei. It has been known for several years that these cortical areas project, instead, to a surrounding area of the brainstem, the paramedian pontine reticular formation; this area has been termed the brainstem saccade generator and, in turn, projects to the oculomotor nuclei. Furthermore , the projection from the frontal cortex to the superior colliculus is not discussed, nor is the direct projection from the retina. This chapter stands in marked contrast to the rest of the book, which is of the highest quality. In future editions, this chapter should be either deleted as unimportant or extensively updated. The second section gives a brief history of theories on the etiology of strabismus and discusses at length examination of the patient. This part is thorough, laden with illustrations and references. The third section discusses …

A case supporting the proposal that cardiac filling pressure is the limiting factor in adjusting to heat stress.

Abstract: Progressively increasing heat stress ultimately results in heat stroke, a medical emergency leading to death if not treated properly. Initially in heat stress, enormous increases in blood flow and volume in skin (and muscle if exercising) are achieved by the diversion of blood away from the splanchnic bed, kidneys, and probably fat and muscle, and in some species such as man, there is also an increase in cardiac output. The onset of heat stroke is thought to involve a decrease in central venous pressure, which is defended by constriction in both arterioles and veins of the skin via low-pressure baroreceptors in the cardiopulmonary region. Body heat loss is thereby reduced and the consequent rise in body temperature causes death due to thermally evoked critical changes in central nervous system activity and/or fatal embolization following disseminated intravascular coagulation and erythrocyte sphering. Evidence is presented, which supports the proposal that cardiac filling pressure is the limiting factor in adjusting to heat stress.